Trial Outcomes & Findings for Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus. (NCT NCT00328627)

NCT ID: NCT00328627

Last Updated: 2013-04-04

Results Overview

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1554 participants
• Primary outcome timeframe: Baseline and Week 26
• Results posted on: 2013-04-04

Participant Flow

Participants took part in the study at 327 investigative sites in 20 countries from 31 May 2006 to 17 March 2008.

Participants with a diagnosis of type 2 diabetes who were inadequately controlled on a regimen of metformin alone were equally randomized to 1 of 12 double-blind treatment groups.

Participant milestones

Measure	Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Placebo Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Placebo Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study STARTED	129	128	129	130	130	130	129	130	130	129	130	130
Overall Study Safety Set	129	128	129	129	130	130	129	130	130	129	130	130
Overall Study COMPLETED	70	97	101	93	115	110	94	116	113	97	112	114
Overall Study NOT COMPLETED	59	31	28	37	15	20	35	14	17	32	18	16

Reasons for withdrawal

Measure	Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Placebo Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Placebo Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Overall Study Hyperglycemic Rescue	41	18	16	13	6	5	19	6	6	11	3	2
Overall Study Adverse Event	3	1	2	3	1	2	1	2	0	7	5	4
Overall Study Protocol Violation	2	2	2	8	5	5	6	2	1	4	6	2
Overall Study Lost to Follow-up	4	2	2	4	0	2	3	0	3	2	0	1
Overall Study Withdrawal by Subject	5	4	5	6	2	5	4	4	4	5	2	7
Overall Study Pregnancy	0	1	0	0	0	0	0	0	0	0	0	0
Overall Study Physician Decision	4	3	1	2	1	1	1	0	3	2	1	0
Overall Study Other	0	0	0	1	0	0	1	0	0	1	1	0

Baseline Characteristics

Efficacy and Safety of Alogliptin Combined With Pioglitazone in Treating Subjects With Type 2 Diabetes Mellitus.

Baseline characteristics by cohort

Measure	Placebo n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Placebo n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Placebo n=129 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 15 n=130 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Total n=1554 Participants Total of all reporting groups
Age Continuous	55.2 years STANDARD_DEVIATION 9.89 • n=93 Participants	53.1 years STANDARD_DEVIATION 9.59 • n=4 Participants	53.7 years STANDARD_DEVIATION 9.31 • n=27 Participants	54.1 years STANDARD_DEVIATION 9.54 • n=483 Participants	53.6 years STANDARD_DEVIATION 9.91 • n=36 Participants	54.9 years STANDARD_DEVIATION 9.18 • n=10 Participants	56.1 years STANDARD_DEVIATION 9.43 • n=115 Participants	55.0 years STANDARD_DEVIATION 9.07 • n=40 Participants	54.4 years STANDARD_DEVIATION 9.69 • n=8 Participants	54.5 years STANDARD_DEVIATION 9.70 • n=62 Participants	54.0 years STANDARD_DEVIATION 9.82 • n=95 Participants	54.2 years STANDARD_DEVIATION 8.86 • n=129 Participants	54.4 years STANDARD_DEVIATION 9.50 • n=36 Participants
Age, Customized <65 years	106 participants n=93 Participants	116 participants n=4 Participants	112 participants n=27 Participants	113 participants n=483 Participants	109 participants n=36 Participants	112 participants n=10 Participants	101 participants n=115 Participants	111 participants n=40 Participants	107 participants n=8 Participants	112 participants n=62 Participants	111 participants n=95 Participants	112 participants n=129 Participants	1322 participants n=36 Participants
Age, Customized ≥65 years	23 participants n=93 Participants	12 participants n=4 Participants	17 participants n=27 Participants	17 participants n=483 Participants	21 participants n=36 Participants	18 participants n=10 Participants	28 participants n=115 Participants	19 participants n=40 Participants	23 participants n=8 Participants	17 participants n=62 Participants	19 participants n=95 Participants	18 participants n=129 Participants	232 participants n=36 Participants
Sex: Female, Male Female	68 Participants n=93 Participants	61 Participants n=4 Participants	79 Participants n=27 Participants	69 Participants n=483 Participants	70 Participants n=36 Participants	69 Participants n=10 Participants	66 Participants n=115 Participants	76 Participants n=40 Participants	75 Participants n=8 Participants	76 Participants n=62 Participants	70 Participants n=95 Participants	78 Participants n=129 Participants	857 Participants n=36 Participants
Sex: Female, Male Male	61 Participants n=93 Participants	67 Participants n=4 Participants	50 Participants n=27 Participants	61 Participants n=483 Participants	60 Participants n=36 Participants	61 Participants n=10 Participants	63 Participants n=115 Participants	54 Participants n=40 Participants	55 Participants n=8 Participants	53 Participants n=62 Participants	60 Participants n=95 Participants	52 Participants n=129 Participants	697 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	63 Participants n=93 Participants	60 Participants n=4 Participants	63 Participants n=27 Participants	63 Participants n=483 Participants	55 Participants n=36 Participants	57 Participants n=10 Participants	67 Participants n=115 Participants	66 Participants n=40 Participants	62 Participants n=8 Participants	61 Participants n=62 Participants	63 Participants n=95 Participants	65 Participants n=129 Participants	745 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=93 Participants	68 Participants n=4 Participants	66 Participants n=27 Participants	67 Participants n=483 Participants	75 Participants n=36 Participants	73 Participants n=10 Participants	62 Participants n=115 Participants	64 Participants n=40 Participants	68 Participants n=8 Participants	68 Participants n=62 Participants	67 Participants n=95 Participants	65 Participants n=129 Participants	809 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants	2 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants	0 Participants n=95 Participants	0 Participants n=129 Participants	5 Participants n=36 Participants
Race (NIH/OMB) Asian	5 Participants n=93 Participants	14 Participants n=4 Participants	15 Participants n=27 Participants	11 Participants n=483 Participants	9 Participants n=36 Participants	7 Participants n=10 Participants	10 Participants n=115 Participants	5 Participants n=40 Participants	12 Participants n=8 Participants	12 Participants n=62 Participants	8 Participants n=95 Participants	12 Participants n=129 Participants	120 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	8 Participants n=93 Participants	6 Participants n=4 Participants	5 Participants n=27 Participants	8 Participants n=483 Participants	4 Participants n=36 Participants	3 Participants n=10 Participants	6 Participants n=115 Participants	2 Participants n=40 Participants	5 Participants n=8 Participants	9 Participants n=62 Participants	9 Participants n=95 Participants	3 Participants n=129 Participants	68 Participants n=36 Participants
Race (NIH/OMB) White	93 Participants n=93 Participants	89 Participants n=4 Participants	80 Participants n=27 Participants	85 Participants n=483 Participants	95 Participants n=36 Participants	96 Participants n=10 Participants	96 Participants n=115 Participants	107 Participants n=40 Participants	85 Participants n=8 Participants	85 Participants n=62 Participants	92 Participants n=95 Participants	93 Participants n=129 Participants	1096 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	23 Participants n=93 Participants	19 Participants n=4 Participants	29 Participants n=27 Participants	26 Participants n=483 Participants	20 Participants n=36 Participants	22 Participants n=10 Participants	17 Participants n=115 Participants	15 Participants n=40 Participants	28 Participants n=8 Participants	23 Participants n=62 Participants	21 Participants n=95 Participants	22 Participants n=129 Participants	265 Participants n=36 Participants
Weight	83.38 kg STANDARD_DEVIATION 18.378 • n=93 Participants	84.63 kg STANDARD_DEVIATION 19.378 • n=4 Participants	83.25 kg STANDARD_DEVIATION 18.326 • n=27 Participants	84.68 kg STANDARD_DEVIATION 18.634 • n=483 Participants	85.95 kg STANDARD_DEVIATION 18.498 • n=36 Participants	82.90 kg STANDARD_DEVIATION 16.570 • n=10 Participants	85.86 kg STANDARD_DEVIATION 20.347 • n=115 Participants	83.68 kg STANDARD_DEVIATION 18.340 • n=40 Participants	85.77 kg STANDARD_DEVIATION 18.844 • n=8 Participants	82.10 kg STANDARD_DEVIATION 17.019 • n=62 Participants	85.01 kg STANDARD_DEVIATION 18.536 • n=95 Participants	82.79 kg STANDARD_DEVIATION 18.768 • n=129 Participants	84.17 kg STANDARD_DEVIATION 18.470 • n=36 Participants
Height	164.48 cm STANDARD_DEVIATION 10.157 • n=93 Participants	164.61 cm STANDARD_DEVIATION 10.614 • n=4 Participants	162.38 cm STANDARD_DEVIATION 9.790 • n=27 Participants	164.25 cm STANDARD_DEVIATION 11.007 • n=483 Participants	164.59 cm STANDARD_DEVIATION 10.841 • n=36 Participants	163.74 cm STANDARD_DEVIATION 10.456 • n=10 Participants	164.59 cm STANDARD_DEVIATION 9.724 • n=115 Participants	163.63 cm STANDARD_DEVIATION 11.036 • n=40 Participants	163.64 cm STANDARD_DEVIATION 9.548 • n=8 Participants	163.14 cm STANDARD_DEVIATION 10.961 • n=62 Participants	163.82 cm STANDARD_DEVIATION 10.708 • n=95 Participants	163.73 cm STANDARD_DEVIATION 11.432 • n=129 Participants	163.88 cm STANDARD_DEVIATION 10.522 • n=36 Participants
Body Mass Index (BMI)	30.59 kg/m^2 STANDARD_DEVIATION 4.808 • n=93 Participants	30.96 kg/m^2 STANDARD_DEVIATION 5.133 • n=4 Participants	31.48 kg/m^2 STANDARD_DEVIATION 5.733 • n=27 Participants	31.25 kg/m^2 STANDARD_DEVIATION 5.280 • n=483 Participants	31.53 kg/m^2 STANDARD_DEVIATION 4.979 • n=36 Participants	30.78 kg/m^2 STANDARD_DEVIATION 4.723 • n=10 Participants	31.41 kg/m^2 STANDARD_DEVIATION 5.391 • n=115 Participants	31.09 kg/m^2 STANDARD_DEVIATION 5.054 • n=40 Participants	31.86 kg/m^2 STANDARD_DEVIATION 5.585 • n=8 Participants	30.69 kg/m^2 STANDARD_DEVIATION 4.721 • n=62 Participants	31.51 kg/m^2 STANDARD_DEVIATION 5.206 • n=95 Participants	30.62 kg/m^2 STANDARD_DEVIATION 4.751 • n=129 Participants	31.15 kg/m^2 STANDARD_DEVIATION 5.122 • n=36 Participants
Diabetes Duration	6.01 years STANDARD_DEVIATION 4.958 • n=93 Participants	6.17 years STANDARD_DEVIATION 5.614 • n=4 Participants	5.55 years STANDARD_DEVIATION 4.879 • n=27 Participants	5.70 years STANDARD_DEVIATION 4.767 • n=483 Participants	6.08 years STANDARD_DEVIATION 5.485 • n=36 Participants	6.86 years STANDARD_DEVIATION 5.489 • n=10 Participants	7.63 years STANDARD_DEVIATION 7.069 • n=115 Participants	5.81 years STANDARD_DEVIATION 5.054 • n=40 Participants	6.63 years STANDARD_DEVIATION 6.005 • n=8 Participants	5.68 years STANDARD_DEVIATION 4.232 • n=62 Participants	6.59 years STANDARD_DEVIATION 5.273 • n=95 Participants	6.22 years STANDARD_DEVIATION 5.014 • n=129 Participants	6.24 years STANDARD_DEVIATION 5.375 • n=36 Participants
Baseline metformin dose	1936.8 mg STANDARD_DEVIATION 428.41 • n=93 Participants	1902.0 mg STANDARD_DEVIATION 450.17 • n=4 Participants	1851.2 mg STANDARD_DEVIATION 413.85 • n=27 Participants	1892.6 mg STANDARD_DEVIATION 410.70 • n=483 Participants	1909.6 mg STANDARD_DEVIATION 418.98 • n=36 Participants	1880.0 mg STANDARD_DEVIATION 413.65 • n=10 Participants	1853.5 mg STANDARD_DEVIATION 435.72 • n=115 Participants	1822.3 mg STANDARD_DEVIATION 444.22 • n=40 Participants	1867.1 mg STANDARD_DEVIATION 455.48 • n=8 Participants	1918.6 mg STANDARD_DEVIATION 417.91 • n=62 Participants	1919.6 mg STANDARD_DEVIATION 421.22 • n=95 Participants	1884.6 mg STANDARD_DEVIATION 439.47 • n=129 Participants	1886.5 mg STANDARD_DEVIATION 429.08 • n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

The primary analysis compared the groupings (combinations of individual treatment groups) of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone (Pioglitazone Alone).

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=376 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=385 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=377 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c) (Grouped Analysis)	—	—	—	—	—	—	—	—	-0.89 percentage of glycosylated hemoglobin Standard Error 0.046	-1.43 percentage of glycosylated hemoglobin Standard Error 0.046	-1.42 percentage of glycosylated hemoglobin Standard Error 0.046	—

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=126 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in HbA1c	-1.34 percentage of glycosylated hemoglobin Standard Error 0.078	-1.27 percentage of glycosylated hemoglobin Standard Error 0.079	-0.92 percentage of glycosylated hemoglobin Standard Error 0.081	-1.39 percentage of glycosylated hemoglobin Standard Error 0.079	-1.39 percentage of glycosylated hemoglobin Standard Error 0.080	-1.00 percentage of glycosylated hemoglobin Standard Error 0.080	-1.55 percentage of glycosylated hemoglobin Standard Error 0.079	-1.60 percentage of glycosylated hemoglobin Standard Error 0.080	-0.13 percentage of glycosylated hemoglobin Standard Error 0.080	-0.64 percentage of glycosylated hemoglobin Standard Error 0.081	-0.90 percentage of glycosylated hemoglobin Standard Error 0.081	-0.75 percentage of glycosylated hemoglobin Standard Error 0.079

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16 and 20.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline to Weeks 4, 8, 12, 16 and 20 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as class variables, and baseline metformin dose and HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in HbA1c Over Time (Grouped Analysis) Week 8 (n=376, 385, 377)	—	—	—	—	—	—	—	—	-0.61 percentage of glycosylated hemoglobin Standard Error 0.034	-1.06 percentage of glycosylated hemoglobin Standard Error 0.033	-1.09 percentage of glycosylated hemoglobin Standard Error 0.034	—
Change From Baseline in HbA1c Over Time (Grouped Analysis) Week 4 (n=345, 359, 346)	—	—	—	—	—	—	—	—	-0.32 percentage of glycosylated hemoglobin Standard Error 0.023	-0.57 percentage of glycosylated hemoglobin Standard Error 0.023	-0.61 percentage of glycosylated hemoglobin Standard Error 0.023	—
Change From Baseline in HbA1c Over Time (Grouped Analysis) Week 12 (n=376, 385, 377)	—	—	—	—	—	—	—	—	-0.81 percentage of glycosylated hemoglobin Standard Error 0.039	-1.29 percentage of glycosylated hemoglobin Standard Error 0.039	-1.38 percentage of glycosylated hemoglobin Standard Error 0.039	—
Change From Baseline in HbA1c Over Time (Grouped Analysis) Week 16 (n=376, 385, 377)	—	—	—	—	—	—	—	—	-0.92 percentage of glycosylated hemoglobin Standard Error 0.041	-1.44 percentage of glycosylated hemoglobin Standard Error 0.041	-1.49 percentage of glycosylated hemoglobin Standard Error 0.041	—
Change From Baseline in HbA1c Over Time (Grouped Analysis) Week 20 (n=376, 385, 377)	—	—	—	—	—	—	—	—	-0.92 percentage of glycosylated hemoglobin Standard Error 0.043	-1.46 percentage of glycosylated hemoglobin Standard Error 0.042	-1.51 percentage of glycosylated hemoglobin Standard Error 0.043	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 4. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=115 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=117 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=112 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=110 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in HbA1c	-0.53 percentage of glycosylated hemoglobin Standard Error 0.039	-0.61 percentage of glycosylated hemoglobin Standard Error 0.040	-0.24 percentage of glycosylated hemoglobin Standard Error 0.040	-0.60 percentage of glycosylated hemoglobin Standard Error 0.039	-0.60 percentage of glycosylated hemoglobin Standard Error 0.039	-0.40 percentage of glycosylated hemoglobin Standard Error 0.040	-0.58 percentage of glycosylated hemoglobin Standard Error 0.040	-0.63 percentage of glycosylated hemoglobin Standard Error 0.040	-0.22 percentage of glycosylated hemoglobin Standard Error 0.039	-0.46 percentage of glycosylated hemoglobin Standard Error 0.040	-0.51 percentage of glycosylated hemoglobin Standard Error 0.041	-0.32 percentage of glycosylated hemoglobin Standard Error 0.040

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 8. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=126 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in HbA1c	-1.01 percentage of glycosylated hemoglobin Standard Error 0.058	-1.04 percentage of glycosylated hemoglobin Standard Error 0.058	-0.57 percentage of glycosylated hemoglobin Standard Error 0.059	-1.05 percentage of glycosylated hemoglobin Standard Error 0.058	-1.02 percentage of glycosylated hemoglobin Standard Error 0.059	-0.76 percentage of glycosylated hemoglobin Standard Error 0.058	-1.11 percentage of glycosylated hemoglobin Standard Error 0.058	-1.20 percentage of glycosylated hemoglobin Standard Error 0.058	-0.30 percentage of glycosylated hemoglobin Standard Error 0.058	-0.75 percentage of glycosylated hemoglobin Standard Error 0.059	-0.80 percentage of glycosylated hemoglobin Standard Error 0.059	-0.50 percentage of glycosylated hemoglobin Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 12.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=126 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in HbA1c	-1.24 percentage of glycosylated hemoglobin Standard Error 0.066	-1.26 percentage of glycosylated hemoglobin Standard Error 0.067	-0.77 percentage of glycosylated hemoglobin Standard Error 0.068	-1.29 percentage of glycosylated hemoglobin Standard Error 0.067	-1.33 percentage of glycosylated hemoglobin Standard Error 0.068	-1.02 percentage of glycosylated hemoglobin Standard Error 0.067	-1.34 percentage of glycosylated hemoglobin Standard Error 0.067	-1.53 percentage of glycosylated hemoglobin Standard Error 0.067	-0.28 percentage of glycosylated hemoglobin Standard Error 0.067	-0.84 percentage of glycosylated hemoglobin Standard Error 0.069	-0.92 percentage of glycosylated hemoglobin Standard Error 0.068	-0.65 percentage of glycosylated hemoglobin Standard Error 0.067

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward (LOCF) imputation was utilized.

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 16. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=126 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in HbA1c	-1.36 percentage of glycosylated hemoglobin Standard Error 0.070	-1.36 percentage of glycosylated hemoglobin Standard Error 0.071	-0.91 percentage of glycosylated hemoglobin Standard Error 0.072	-1.42 percentage of glycosylated hemoglobin Standard Error 0.071	-1.45 percentage of glycosylated hemoglobin Standard Error 0.072	-1.12 percentage of glycosylated hemoglobin Standard Error 0.071	-1.53 percentage of glycosylated hemoglobin Standard Error 0.071	-1.66 percentage of glycosylated hemoglobin Standard Error 0.071	-0.27 percentage of glycosylated hemoglobin Standard Error 0.071	-0.82 percentage of glycosylated hemoglobin Standard Error 0.072	-1.03 percentage of glycosylated hemoglobin Standard Error 0.072	-0.74 percentage of glycosylated hemoglobin Standard Error 0.071

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at week 20.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HbA1c as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=126 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in HbA1c	-1.39 percentage of glycosylated hemoglobin Standard Error 0.073	-1.37 percentage of glycosylated hemoglobin Standard Error 0.074	-0.90 percentage of glycosylated hemoglobin Standard Error 0.075	-1.43 percentage of glycosylated hemoglobin Standard Error 0.074	-1.49 percentage of glycosylated hemoglobin Standard Error 0.075	-1.10 percentage of glycosylated hemoglobin Standard Error 0.074	-1.57 percentage of glycosylated hemoglobin Standard Error 0.074	-1.66 percentage of glycosylated hemoglobin Standard Error 0.074	-0.24 percentage of glycosylated hemoglobin Standard Error 0.074	-0.75 percentage of glycosylated hemoglobin Standard Error 0.075	-0.99 percentage of glycosylated hemoglobin Standard Error 0.075	-0.75 percentage of glycosylated hemoglobin Standard Error 0.074

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in fasting plasma glucose was assessed at weeks 1, 2, 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 1 (n=358, 355, 354)	—	—	—	—	—	—	—	—	-4.1 mg/dL Standard Error 1.56	-22.6 mg/dL Standard Error 1.57	-23.1 mg/dL Standard Error 1.57	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 26 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-28.3 mg/dL Standard Error 2.03	-45.2 mg/dL Standard Error 2.02	-44.2 mg/dL Standard Error 2.03	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 2 (n=379, 383, 381)	—	—	—	—	—	—	—	—	-11.3 mg/dL Standard Error 1.62	-30.3 mg/dL Standard Error 1.61	-31.6 mg/dL Standard Error 1.62	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 4 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-19.9 mg/dL Standard Error 1.67	-36.8 mg/dL Standard Error 1.66	-39.8 mg/dL Standard Error 1.67	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 8 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-27.3 mg/dL Standard Error 1.77	-42.3 mg/dL Standard Error 1.76	-45.2 mg/dL Standard Error 1.77	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 12 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-30.3 mg/dL Standard Error 1.84	-45.0 mg/dL Standard Error 1.83	-47.6 mg/dL Standard Error 1.83	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 16 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-27.9 mg/dL Standard Error 1.86	-43.7 mg/dL Standard Error 1.85	-45.4 mg/dL Standard Error 1.86	—
Change From Baseline in Fasting Plasma Glucose Over Time (Grouped Analysis) Week 20 (n=381, 386, 383)	—	—	—	—	—	—	—	—	-28.1 mg/dL Standard Error 2.00	-43.6 mg/dL Standard Error 1.99	-45.0 mg/dL Standard Error 1.99	—

SECONDARY outcome

Timeframe: Baseline and Week 1

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=113 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=123 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=117 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 1 in Fasting Plasma Glucose	-21.3 mg/dL Standard Error 2.69	-20.9 mg/dL Standard Error 2.66	0.4 mg/dL Standard Error 2.73	-23.2 mg/dL Standard Error 2.71	-23.2 mg/dL Standard Error 2.72	-6.7 mg/dL Standard Error 2.69	-23.2 mg/dL Standard Error 2.76	-25.0 mg/dL Standard Error 2.78	1.8 mg/dL Standard Error 2.67	-14.5 mg/dL Standard Error 2.77	-18.6 mg/dL Standard Error 2.73	-6.1 mg/dL Standard Error 2.70

SECONDARY outcome

Timeframe: Baseline and Week 2

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=129 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=128 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=125 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 2 in Fasting Plasma Glucose	-30.1 mg/dL Standard Error 2.80	-31.7 mg/dL Standard Error 2.78	-4.3 mg/dL Standard Error 2.83	-30.0 mg/dL Standard Error 2.79	-31.3 mg/dL Standard Error 2.81	-19.3 mg/dL Standard Error 2.79	-30.8 mg/dL Standard Error 2.79	-31.7 mg/dL Standard Error 2.81	4.8 mg/dL Standard Error 2.78	-21.9 mg/dL Standard Error 2.88	-18.9 mg/dL Standard Error 2.82	-10.4 mg/dL Standard Error 2.80

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=125 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Fasting Plasma Glucose	-35.3 mg/dL Standard Error 2.87	-37.3 mg/dL Standard Error 2.86	-13.4 mg/dL Standard Error 2.92	-37.4 mg/dL Standard Error 2.88	-36.0 mg/dL Standard Error 2.91	-26.1 mg/dL Standard Error 2.87	-37.8 mg/dL Standard Error 2.89	-46.2 mg/dL Standard Error 2.89	3.8 mg/dL Standard Error 2.87	-20.4 mg/dL Standard Error 2.95	-22.8 mg/dL Standard Error 2.92	-20.2 mg/dL Standard Error 2.90

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Fasting Plasma Glucose	-42.3 mg/dL Standard Error 3.05	-39.3 mg/dL Standard Error 3.04	-24.0 mg/dL Standard Error 3.10	-40.5 mg/dL Standard Error 3.05	-44.1 mg/dL Standard Error 3.08	-35.6 mg/dL Standard Error 3.05	-44.0 mg/dL Standard Error 3.06	-52.3 mg/dL Standard Error 3.07	5.7 mg/dL Standard Error 3.05	-19.5 mg/dL Standard Error 3.14	-19.3 mg/dL Standard Error 3.09	-22.2 mg/dL Standard Error 3.07

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Fasting Plasma Glucose	-42.9 mg/dL Standard Error 3.16	-42.5 mg/dL Standard Error 3.14	-26.6 mg/dL Standard Error 3.21	-42.8 mg/dL Standard Error 3.16	-49.0 mg/dL Standard Error 3.19	-41.3 mg/dL Standard Error 3.16	-49.2 mg/dL Standard Error 3.17	-51.4 mg/dL Standard Error 3.18	3.4 mg/dL Standard Error 3.16	-19.3 mg/dL Standard Error 3.25	-23.3 mg/dL Standard Error 3.19	-23.0 mg/dL Standard Error 3.18

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Fasting Plasma Glucose	-41.6 mg/dL Standard Error 3.20	-39.1 mg/dL Standard Error 3.19	-26.3 mg/dL Standard Error 3.25	-41.5 mg/dL Standard Error 3.20	-43.4 mg/dL Standard Error 3.24	-36.3 mg/dL Standard Error 3.20	-47.9 mg/dL Standard Error 3.21	-53.8 mg/dL Standard Error 3.22	1.4 mg/dL Standard Error 3.20	-16.2 mg/dL Standard Error 3.29	-22.6 mg/dL Standard Error 3.24	-21.2 mg/dL Standard Error 3.22

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Fasting Plasma Glucose	-43.0 mg/dL Standard Error 3.43	-39.3 mg/dL Standard Error 3.42	-26.3 mg/dL Standard Error 3.49	-41.1 mg/dL Standard Error 3.44	-43.1 mg/dL Standard Error 3.47	-35.7 mg/dL Standard Error 3.43	-46.8 mg/dL Standard Error 3.45	-52.4 mg/dL Standard Error 3.46	6.7 mg/dL Standard Error 3.43	-8.7 mg/dL Standard Error 3.53	-23.5 mg/dL Standard Error 3.48	-22.4 mg/dL Standard Error 3.46

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline fasting plasma glucose as covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Fasting Plasma Glucose	-42.0 mg/dL Standard Error 3.50	-38.0 mg/dL Standard Error 3.48	-28.8 mg/dL Standard Error 3.55	-42.2 mg/dL Standard Error 3.50	-41.7 mg/dL Standard Error 3.54	-32.4 mg/dL Standard Error 3.49	-51.3 mg/dL Standard Error 3.51	-52.7 mg/dL Standard Error 3.52	6.5 mg/dL Standard Error 3.50	-13.2 mg/dL Standard Error 3.59	-18.6 mg/dL Standard Error 3.54	-23.6 mg/dL Standard Error 3.52

SECONDARY outcome

Timeframe: From Week 1 to Week 26

Population: Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.

Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=381 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=386 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=384 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Marked Hyperglycemia (Grouped Analysis)	—	—	—	—	—	—	—	—	39.4 percentage of participants	24.6 percentage of participants	22.1 percentage of participants	—

SECONDARY outcome

Timeframe: From Week 1 to Week 26

Population: Full analysis set including patients with at least one non-missing fasting plasma glucose result in each treatment group.

Marked hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (11.10 mmol/L).

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=126 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Marked Hyperglycemia	27.1 percentage of participants	22.3 percentage of participants	39.2 percentage of participants	26.4 percentage of participants	23.6 percentage of participants	41.1 percentage of participants	20.3 percentage of participants	20.5 percentage of participants	60.5 percentage of participants	42.6 percentage of participants	39.7 percentage of participants	37.8 percentage of participants

SECONDARY outcome

Timeframe: From Week 1 to Week 26.

Population: Full analysis set including patients with at least 1 postbaseline visit. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:

1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;

2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;

3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;

4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=376 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=382 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=377 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants Meeting Rescue Criteria (Grouped Analysis)	—	—	—	—	—	—	—	—	11.4 percentage of participants	3.9 percentage of participants	3.4 percentage of participants	—

SECONDARY outcome

Timeframe: From Week 1 to Week 26

Population: Full analysis set including patients with at least 1 postbaseline visit.

Rescue was defined as meeting 1 of the following criteria, confirmed by a 2nd sample drawn within 5 days of the first and analyzed by the central laboratory:

1. After the Week 1 Visit but prior to the Week 4 Visit: a single fasting plasma glucose ≥300 mg/dL;

2. From the Week 4 Visit but prior to the Week 8 Visit: a single fasting plasma glucose ≥275 mg/dL;

3. From the Week 8 Visit but prior to the Week 12 Visit: a single fasting plasma glucose ≥250 mg/dL;

4. From the Week 12 Visit through the End-of-Treatment Visit: HbA1c ≥8.5% and ≤0.5% reduction in HbA1c as compared with Baseline HbA1c.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=129 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=129 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=124 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=125 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=127 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants Meeting Rescue Criteria	4.7 percentage of participants	3.9 percentage of participants	15.4 percentage of participants	4.8 percentage of participants	4.9 percentage of participants	8.7 percentage of participants	2.4 percentage of participants	1.6 percentage of participants	32.8 percentage of participants	14.5 percentage of participants	12.8 percentage of participants	10.2 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5% (Grouped Analysis)	—	—	—	—	—	—	—	—	12.4 percentage of participants	27.9 percentage of participants	29.2 percentage of participants	—

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 6.5%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 6.5%	21.5 percentage of participants	24.6 percentage of participants	11.6 percentage of participants	30.0 percentage of participants	30.0 percentage of participants	19.4 percentage of participants	32.3 percentage of participants	33.1 percentage of participants	0.8 percentage of participants	8.6 percentage of participants	12.4 percentage of participants	6.2 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.0% (Grouped Analysis)	—	—	—	—	—	—	—	—	30.5 percentage of participants	54.6 percentage of participants	55.9 percentage of participants	—

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7%	49.2 percentage of participants	54.6 percentage of participants	29.5 percentage of participants	53.1 percentage of participants	53.1 percentage of participants	36.4 percentage of participants	61.5 percentage of participants	60.0 percentage of participants	6.2 percentage of participants	22.7 percentage of participants	27.1 percentage of participants	25.6 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5% (Grouped Analysis)	—	—	—	—	—	—	—	—	54.8 percentage of participants	77.4 percentage of participants	74.1 percentage of participants	—

SECONDARY outcome

Timeframe: Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with HbA1c less than or equal to 7.5%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With Glycosylated Hemoglobin ≤ 7.5%	77.7 percentage of participants	71.5 percentage of participants	55.8 percentage of participants	73.8 percentage of participants	72.3 percentage of participants	56.6 percentage of participants	80.8 percentage of participants	78.5 percentage of participants	24.8 percentage of participants	38.3 percentage of participants	55.0 percentage of participants	51.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5% (Grouped Analysis)	—	—	—	—	—	—	—	—	67.2 percentage of participants	85.6 percentage of participants	83.3 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 0.5%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 0.5%	86.2 percentage of participants	79.2 percentage of participants	68.2 percentage of participants	86.9 percentage of participants	83.8 percentage of participants	72.1 percentage of participants	83.8 percentage of participants	86.9 percentage of participants	31.8 percentage of participants	57.8 percentage of participants	66.7 percentage of participants	61.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1% (Grouped Analysis)	—	—	—	—	—	—	—	—	45.7 percentage of participants	71.8 percentage of participants	69.5 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1%	69.2 percentage of participants	66.9 percentage of participants	46.5 percentage of participants	73.1 percentage of participants	69.2 percentage of participants	54.3 percentage of participants	73.1 percentage of participants	72.3 percentage of participants	16.3 percentage of participants	33.6 percentage of participants	47.3 percentage of participants	36.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5% (Grouped Analysis)	—	—	—	—	—	—	—	—	27.6 percentage of participants	45.9 percentage of participants	50.3 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 1.5%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 1.5%	41.5 percentage of participants	46.2 percentage of participants	27.1 percentage of participants	45.4 percentage of participants	46.2 percentage of participants	34.1 percentage of participants	50.8 percentage of participants	58.5 percentage of participants	5.4 percentage of participants	15.6 percentage of participants	28.7 percentage of participants	21.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 26.

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2.0%.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2.0% (Grouped Analysis)	—	—	—	—	—	—	—	—	11.1 percentage of participants	25.4 percentage of participants	27.7 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: The full analysis set. Patients who did not complete the scheduled Week 26 visit were assessed based on their response at the time of discontinuation.

Clinical response at Week 26 was assessed by the percentage of participants with a decrease from Baseline in HbA1c of greater than or equal to 2%.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=129 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=128 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=129 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=129 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Percentage of Participants With a Decrease in Glycosylated Hemoglobin ≥ 2%	23.1 percentage of participants	21.5 percentage of participants	9.3 percentage of participants	22.3 percentage of participants	26.2 percentage of participants	17.1 percentage of participants	30.8 percentage of participants	35.4 percentage of participants	1.6 percentage of participants	7.8 percentage of participants	11.6 percentage of participants	7.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin was assessed at Weeks 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 8 (n=357, 347, 358)	—	—	—	—	—	—	—	—	-7.2 pmol/L Standard Error 0.87	-11.3 pmol/L Standard Error 0.88	-11.3 pmol/L Standard Error 0.87	—
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 12 (n=357, 347, 358)	—	—	—	—	—	—	—	—	-8.2 pmol/L Standard Error 0.91	-11.6 pmol/L Standard Error 0.93	-11.6 pmol/L Standard Error 0.91	—
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 16 (n=358, 348, 358)	—	—	—	—	—	—	—	—	-7.2 pmol/L Standard Error 0.92	-12.2 pmol/L Standard Error 0.94	-11.3 pmol/L Standard Error 0.92	—
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 20 (n=358, 349, 359)	—	—	—	—	—	—	—	—	-6.6 pmol/L Standard Error 1.08	-10.4 pmol/L Standard Error 1.09	-10.7 pmol/L Standard Error 1.08	—
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 26 (n=358, 349, 359)	—	—	—	—	—	—	—	—	-5.3 pmol/L Standard Error 1.09	-10.6 pmol/L Standard Error 1.11	-9.5 pmol/L Standard Error 1.09	—
Change From Baseline in Fasting Proinsulin Over Time (Grouped Analysis) Week 4 (n=328, 319, 327)	—	—	—	—	—	—	—	—	-6.2 pmol/L Standard Error 0.81	-10.3 pmol/L Standard Error 0.82	-10.1 pmol/L Standard Error 0.81	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=109 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=109 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=105 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=105 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=104 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=116 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=111 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=109 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=107 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Fasting Proinsulin	-9.9 pmol/L Standard Error 1.41	-8.9 pmol/L Standard Error 1.41	-6.7 pmol/L Standard Error 1.40	-9.6 pmol/L Standard Error 1.43	-9.5 pmol/L Standard Error 1.37	-7.2 pmol/L Standard Error 1.39	-11.3 pmol/L Standard Error 1.43	-11.7 pmol/L Standard Error 1.44	-0.1 pmol/L Standard Error 1.36	-4.7 pmol/L Standard Error 1.39	-2.3 pmol/L Standard Error 1.41	-4.8 pmol/L Standard Error 1.42

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Fasting Proinsulin	-11.1 pmol/L Standard Error 1.50	-10.7 pmol/L Standard Error 1.50	-8.8 pmol/L Standard Error 1.52	-11.8 pmol/L Standard Error 1.54	-9.4 pmol/L Standard Error 1.50	-9.0 pmol/L Standard Error 1.50	-11.0 pmol/L Standard Error 1.53	-13.8 pmol/L Standard Error 1.50	0.7 pmol/L Standard Error 1.48	0.2 pmol/L Standard Error 1.50	-2.6 pmol/L Standard Error 1.48	-3.8 pmol/L Standard Error 1.49

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Fasting Proinsulin	-10.1 pmol/L Standard Error 1.58	-8.8 pmol/L Standard Error 1.58	-11.2 pmol/L Standard Error 1.60	-12.1 pmol/L Standard Error 1.63	-12.7 pmol/L Standard Error 1.58	-8.1 pmol/L Standard Error 1.58	-12.7 pmol/L Standard Error 1.61	-13.2 pmol/L Standard Error 1.58	-1.0 pmol/L Standard Error 1.56	-0.7 pmol/L Standard Error 1.57	-2.3 pmol/L Standard Error 1.56	-5.3 pmol/L Standard Error 1.57

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Fasting Proinsulin	-11.0 pmol/L Standard Error 1.60	-8.4 pmol/L Standard Error 1.60	-10.0 pmol/L Standard Error 1.62	-12.6 pmol/L Standard Error 1.65	-11.2 pmol/L Standard Error 1.60	-8.0 pmol/L Standard Error 1.60	-13.0 pmol/L Standard Error 1.63	-14.4 pmol/L Standard Error 1.60	-3.0 pmol/L Standard Error 1.58	0.0 pmol/L Standard Error 1.60	-2.3 pmol/L Standard Error 1.58	-3.7 pmol/L Standard Error 1.59

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Fasting Proinsulin	-11.2 pmol/L Standard Error 1.86	-8.7 pmol/L Standard Error 1.86	-9.3 pmol/L Standard Error 1.89	-10.0 pmol/L Standard Error 1.92	-10.7 pmol/L Standard Error 1.87	-7.1 pmol/L Standard Error 1.86	-10.2 pmol/L Standard Error 1.90	-12.5 pmol/L Standard Error 1.87	-0.9 pmol/L Standard Error 1.85	1.5 pmol/L Standard Error 1.86	-3.0 pmol/L Standard Error 1.84	-3.4 pmol/L Standard Error 1.86

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Fasting Proinsulin	-10.9 pmol/L Standard Error 1.88	-7.2 pmol/L Standard Error 1.88	-8.4 pmol/L Standard Error 1.91	-8.9 pmol/L Standard Error 1.95	-8.8 pmol/L Standard Error 1.89	-4.1 pmol/L Standard Error 1.89	-12.1 pmol/L Standard Error 1.93	-12.6 pmol/L Standard Error 1.89	1.2 pmol/L Standard Error 1.87	0.7 pmol/L Standard Error 1.88	-3.3 pmol/L Standard Error 1.86	-3.5 pmol/L Standard Error 1.88

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in fasting insulin was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 4 (n=325, 318, 326)	—	—	—	—	—	—	—	—	-2.29 µIU/mL Standard Error 0.440	-2.11 µIU/mL Standard Error 0.445	-2.19 µIU/mL Standard Error 0.440	—
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 8 (n=355, 346, 356)	—	—	—	—	—	—	—	—	-2.35 µIU/mL Standard Error 0.535	-2.44 µIU/mL Standard Error 0.542	-2.36 µIU/mL Standard Error 0.534	—
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 12 (n=355, 347, 356)	—	—	—	—	—	—	—	—	-2.62 µIU/mL Standard Error 0.498	-1.73 µIU/mL Standard Error 0.503	-2.62 µIU/mL Standard Error 0.497	—
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 16 (n=356, 348, 356)	—	—	—	—	—	—	—	—	-2.19 µIU/mL Standard Error 0.488	-2.60 µIU/mL Standard Error 0.494	-2.48 µIU/mL Standard Error 0.488	—
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 20 (n=356, 349, 357)	—	—	—	—	—	—	—	—	-2.35 µIU/mL Standard Error 0.511	-1.91 µIU/mL Standard Error 0.516	-2.06 µIU/mL Standard Error 0.510	—
Change From Baseline in Insulin Over Time (Grouped Analysis) Week 26 (n=356, 349, 357)	—	—	—	—	—	—	—	—	-1.74 µIU/mL Standard Error 1.212	-2.05 µIU/mL Standard Error 1.225	-1.66 µIU/mL Standard Error 1.210	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=109 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=108 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=104 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=105 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=104 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=116 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=110 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=106 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=107 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Insulin Levels	-3.03 µIU/mL Standard Error 0.760	-1.86 µIU/mL Standard Error 0.763	-2.43 µIU/mL Standard Error 0.760	-1.45 µIU/mL Standard Error 0.779	-2.05 µIU/mL Standard Error 0.743	-2.76 µIU/mL Standard Error 0.760	-1.85 µIU/mL Standard Error 0.774	-2.65 µIU/mL Standard Error 0.778	1.06 µIU/mL Standard Error 0.737	-0.33 µIU/mL Standard Error 0.756	2.31 µIU/mL Standard Error 0.771	-1.68 µIU/mL Standard Error 0.767

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=112 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Insulin Levels	-2.21 µIU/mL Standard Error 0.923	-2.78 µIU/mL Standard Error 0.923	-2.74 µIU/mL Standard Error 0.935	-3.15 µIU/mL Standard Error 0.953	-1.20 µIU/mL Standard Error 0.927	-2.83 µIU/mL Standard Error 0.927	-1.96 µIU/mL Standard Error 0.939	-3.09 µIU/mL Standard Error 0.924	-0.46 µIU/mL Standard Error 0.912	1.80 µIU/mL Standard Error 0.923	1.69 µIU/mL Standard Error 0.909	-1.47 µIU/mL Standard Error 0.916

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Insulin Levels	-1.47 µIU/mL Standard Error 0.859	-2.01 µIU/mL Standard Error 0.859	-3.61 µIU/mL Standard Error 0.870	-1.36 µIU/mL Standard Error 0.882	-2.83 µIU/mL Standard Error 0.863	-2.95 µIU/mL Standard Error 0.863	-2.35 µIU/mL Standard Error 0.874	-3.01 µIU/mL Standard Error 0.859	0.06 µIU/mL Standard Error 0.849	1.79 µIU/mL Standard Error 0.859	1.93 µIU/mL Standard Error 0.846	-1.29 µIU/mL Standard Error 0.852

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Insulin Levels	-2.28 µIU/mL Standard Error 0.840	-1.11 µIU/mL Standard Error 0.843	-3.46 µIU/mL Standard Error 0.851	-2.50 µIU/mL Standard Error 0.866	-2.82 µIU/mL Standard Error 0.847	-2.48 µIU/mL Standard Error 0.847	-3.00 µIU/mL Standard Error 0.858	-3.52 µIU/mL Standard Error 0.844	0.34 µIU/mL Standard Error 0.833	1.22 µIU/mL Standard Error 0.843	1.83 µIU/mL Standard Error 0.830	-0.63 µIU/mL Standard Error 0.836

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Insulin Levels	-2.35 µIU/mL Standard Error 0.876	-0.90 µIU/mL Standard Error 0.880	-3.29 µIU/mL Standard Error 0.891	-2.20 µIU/mL Standard Error 0.907	-2.29 µIU/mL Standard Error 0.887	-3.12 µIU/mL Standard Error 0.887	-1.16 µIU/mL Standard Error 0.899	-3.01 µIU/mL Standard Error 0.884	0.18 µIU/mL Standard Error 0.873	2.03 µIU/mL Standard Error 0.883	0.76 µIU/mL Standard Error 0.869	-0.66 µIU/mL Standard Error 0.876

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline insulin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Insulin Levels	-3.05 µIU/mL Standard Error 2.078	-0.76 µIU/mL Standard Error 2.087	-2.56 µIU/mL Standard Error 2.114	-0.76 µIU/mL Standard Error 2.152	-1.42 µIU/mL Standard Error 2.105	-1.88 µIU/mL Standard Error 2.105	-2.33 µIU/mL Standard Error 2.132	-2.79 µIU/mL Standard Error 2.096	6.78 µIU/mL Standard Error 2.071	1.33 µIU/mL Standard Error 2.096	1.43 µIU/mL Standard Error 2.063	-0.78 µIU/mL Standard Error 2.078

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL) at weeks 4, 8, 12, 16, 20 and 26 relative to the Baseline value.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 4 (n=325, 315, 326)	—	—	—	—	—	—	—	—	-0.021 ratio Standard Error 0.0088	-0.078 ratio Standard Error 0.0089	-0.057 ratio Standard Error 0.0088	—
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 8 (n=355, 344, 356)	—	—	—	—	—	—	—	—	-0.019 ratio Standard Error 0.0084	-0.079 ratio Standard Error 0.0086	-0.081 ratio Standard Error 0.0084	—
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 12 (n=355, 345, 356)	—	—	—	—	—	—	—	—	-0.042 ratio Standard Error 0.0083	-0.086 ratio Standard Error 0.0084	-0.082 ratio Standard Error 0.0083	—
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 16 (n=356, 346, 356)	—	—	—	—	—	—	—	—	-0.033 ratio Standard Error 0.0077	-0.091 ratio Standard Error 0.0078	-0.077 ratio Standard Error 0.0077	—
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 26 (n=356, 347, 357)	—	—	—	—	—	—	—	—	-0.027 ratio Standard Error 0.0088	-0.087 ratio Standard Error 0.0090	-0.076 ratio Standard Error 0.0088	—
Change From Baseline in Proinsulin/Insulin Ratio Over Time (Grouped Analysis) Week 20 (n=356, 347, 357)	—	—	—	—	—	—	—	—	-0.034 ratio Standard Error 0.0076	-0.088 ratio Standard Error 0.0077	-0.078 ratio Standard Error 0.0076	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=108 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=108 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=102 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=105 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=104 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=116 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=110 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=106 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=107 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Proinsulin/Insulin Ratio	-0.054 ratio Standard Error 0.0153	-0.054 ratio Standard Error 0.0153	-0.023 ratio Standard Error 0.0152	-0.068 ratio Standard Error 0.0157	-0.045 ratio Standard Error 0.0149	-0.009 ratio Standard Error 0.0152	-0.111 ratio Standard Error 0.0155	-0.072 ratio Standard Error 0.0156	-0.015 ratio Standard Error 0.0147	-0.039 ratio Standard Error 0.0151	-0.058 ratio Standard Error 0.0154	-0.029 ratio Standard Error 0.0153

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=110 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Proinsulin/Insulin Ratio	-0.086 ratio Standard Error 0.0146	-0.077 ratio Standard Error 0.0146	-0.036 ratio Standard Error 0.0148	-0.054 ratio Standard Error 0.0152	-0.072 ratio Standard Error 0.0146	-0.013 ratio Standard Error 0.0146	-0.098 ratio Standard Error 0.0148	-0.093 ratio Standard Error 0.0146	0.005 ratio Standard Error 0.0144	-0.025 ratio Standard Error 0.0146	-0.045 ratio Standard Error 0.0143	-0.007 ratio Standard Error 0.0144

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Proinsulin/Insulin Ratio	-0.073 ratio Standard Error 0.0144	-0.056 ratio Standard Error 0.0144	-0.063 ratio Standard Error 0.0146	-0.072 ratio Standard Error 0.0149	-0.088 ratio Standard Error 0.0144	-0.021 ratio Standard Error 0.0144	-0.112 ratio Standard Error 0.0146	-0.101 ratio Standard Error 0.0144	-0.006 ratio Standard Error 0.0142	-0.024 ratio Standard Error 0.0144	-0.041 ratio Standard Error 0.0141	-0.041 ratio Standard Error 0.0142

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Proinsulin/Insulin Ratio	-0.078 ratio Standard Error 0.0133	-0.066 ratio Standard Error 0.0134	-0.035 ratio Standard Error 0.0135	-0.094 ratio Standard Error 0.0138	-0.061 ratio Standard Error 0.0134	-0.030 ratio Standard Error 0.0134	-0.102 ratio Standard Error 0.0136	-0.104 ratio Standard Error 0.0133	-0.026 ratio Standard Error 0.0132	-0.036 ratio Standard Error 0.0133	-0.046 ratio Standard Error 0.0131	-0.035 ratio Standard Error 0.0132

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Proinsulin/Insulin Ratio	-0.081 ratio Standard Error 0.0131	-0.065 ratio Standard Error 0.0132	-0.042 ratio Standard Error 0.0133	-0.085 ratio Standard Error 0.0137	-0.077 ratio Standard Error 0.0133	-0.020 ratio Standard Error 0.0133	-0.099 ratio Standard Error 0.0134	-0.092 ratio Standard Error 0.0132	-0.007 ratio Standard Error 0.0131	-0.014 ratio Standard Error 0.0132	-0.046 ratio Standard Error 0.0130	-0.039 ratio Standard Error 0.0131

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The ratio of proinsulin to insulin was calculated as proinsulin (pmol/L) / insulin (μIU/mL).

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline proinsulin/insulin ratio as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=111 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Proinsulin/Insulin Ratio	-0.071 ratio Standard Error 0.0152	-0.063 ratio Standard Error 0.0152	-0.030 ratio Standard Error 0.0154	-0.081 ratio Standard Error 0.0159	-0.072 ratio Standard Error 0.0154	-0.014 ratio Standard Error 0.0154	-0.109 ratio Standard Error 0.0156	-0.092 ratio Standard Error 0.0153	-0.007 ratio Standard Error 0.0151	-0.001 ratio Standard Error 0.0153	-0.064 ratio Standard Error 0.0151	-0.038 ratio Standard Error 0.0152

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline was assessed at Weeks 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 4 (n=335, 335, 336)	—	—	—	—	—	—	—	—	-0.292 ng/mL Standard Error 0.0417	-0.255 ng/mL Standard Error 0.0417	-0.282 ng/mL Standard Error 0.0416	—
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 16 (n=369, 374, 374)	—	—	—	—	—	—	—	—	-0.352 ng/mL Standard Error 0.0456	-0.343 ng/mL Standard Error 0.0453	-0.333 ng/mL Standard Error 0.0453	—
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 26 (n=371, 378, 375)	—	—	—	—	—	—	—	—	-0.341 ng/mL Standard Error 0.0460	-0.346 ng/mL Standard Error 0.0456	-0.326 ng/mL Standard Error 0.0457	—
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 8 (n=367, 366, 371)	—	—	—	—	—	—	—	—	-0.356 ng/mL Standard Error 0.0464	-0.327 ng/mL Standard Error 0.0464	-0.311 ng/mL Standard Error 0.0461	—
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 12 (n=367, 369, 374)	—	—	—	—	—	—	—	—	-0.268 ng/mL Standard Error 0.0781	-0.249 ng/mL Standard Error 0.0779	-0.334 ng/mL Standard Error 0.0774	—
Change From Baseline in C-peptide Over Time (Grouped Analysis) Week 20 (n=369, 375, 375)	—	—	—	—	—	—	—	—	-0.360 ng/mL Standard Error 0.0465	-0.350 ng/mL Standard Error 0.0461	-0.293 ng/mL Standard Error 0.0461	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=112 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=108 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=107 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=117 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=110 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=108 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in C-peptide Levels	-0.248 ng/mL Standard Error 0.0714	-0.238 ng/mL Standard Error 0.0720	-0.232 ng/mL Standard Error 0.0721	-0.259 ng/mL Standard Error 0.0718	-0.268 ng/mL Standard Error 0.0705	-0.393 ng/mL Standard Error 0.0714	-0.252 ng/mL Standard Error 0.0734	-0.337 ng/mL Standard Error 0.0738	0.002 ng/mL Standard Error 0.0705	-0.032 ng/mL Standard Error 0.0727	0.076 ng/mL Standard Error 0.0734	-0.246 ng/mL Standard Error 0.0730

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=124 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in C-peptide Levels	-0.315 ng/mL Standard Error 0.0798	-0.261 ng/mL Standard Error 0.0801	-0.380 ng/mL Standard Error 0.0814	-0.365 ng/mL Standard Error 0.0802	-0.207 ng/mL Standard Error 0.0797	-0.467 ng/mL Standard Error 0.0798	-0.300 ng/mL Standard Error 0.0814	-0.464 ng/mL Standard Error 0.0798	-0.044 ng/mL Standard Error 0.0798	0.114 ng/mL Standard Error 0.0807	0.108 ng/mL Standard Error 0.0801	-0.221 ng/mL Standard Error 0.0798

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in C-peptide Levels	-0.155 ng/mL Standard Error 0.1344	-0.215 ng/mL Standard Error 0.1338	-0.439 ng/mL Standard Error 0.1372	-0.212 ng/mL Standard Error 0.1345	-0.326 ng/mL Standard Error 0.1343	-0.483 ng/mL Standard Error 0.1344	-0.381 ng/mL Standard Error 0.1360	-0.464 ng/mL Standard Error 0.1339	-0.055 ng/mL Standard Error 0.1338	0.083 ng/mL Standard Error 0.1360	0.140 ng/mL Standard Error 0.1349	0.116 ng/mL Standard Error 0.1344

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in C-peptide Levels	-0.282 ng/mL Standard Error 0.0780	-0.184 ng/mL Standard Error 0.0783	-0.410 ng/mL Standard Error 0.0796	-0.318 ng/mL Standard Error 0.0783	-0.306 ng/mL Standard Error 0.0786	-0.404 ng/mL Standard Error 0.0786	-0.431 ng/mL Standard Error 0.0789	-0.510 ng/mL Standard Error 0.0783	-0.076 ng/mL Standard Error 0.0783	0.032 ng/mL Standard Error 0.0796	0.101 ng/mL Standard Error 0.0789	-0.242 ng/mL Standard Error 0.0786

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in C-peptide Levels	-0.377 ng/mL Standard Error 0.0792	-0.184 ng/mL Standard Error 0.0795	-0.380 ng/mL Standard Error 0.0812	-0.343 ng/mL Standard Error 0.0799	-0.266 ng/mL Standard Error 0.0802	-0.506 ng/mL Standard Error 0.0802	-0.329 ng/mL Standard Error 0.0805	-0.430 ng/mL Standard Error 0.0799	-0.046 ng/mL Standard Error 0.0799	0.114 ng/mL Standard Error 0.0812	0.019 ng/mL Standard Error 0.0805	-0.193 ng/mL Standard Error 0.0802

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline C-peptide as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in C-peptide Levels	-0.380 ng/mL Standard Error 0.0783	-0.204 ng/mL Standard Error 0.0789	-0.353 ng/mL Standard Error 0.0805	-0.235 ng/mL Standard Error 0.0790	-0.300 ng/mL Standard Error 0.0795	-0.429 ng/mL Standard Error 0.0793	-0.421 ng/mL Standard Error 0.0796	-0.474 ng/mL Standard Error 0.0793	-0.011 ng/mL Standard Error 0.0793	0.000 ng/mL Standard Error 0.0802	0.059 ng/mL Standard Error 0.0799	-0.239 ng/mL Standard Error 0.0792

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in total cholesterol was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 4 (n=345, 354, 348)	—	—	—	—	—	—	—	—	1.6 mg/dL Standard Error 1.41	-4.3 mg/dL Standard Error 1.39	-6.5 mg/dL Standard Error 1.40	—
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 12 (n=374, 380, 376)	—	—	—	—	—	—	—	—	6.6 mg/dL Standard Error 1.47	1.3 mg/dL Standard Error 1.46	-1.7 mg/dL Standard Error 1.46	—
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 20 (n=374, 380, 376)	—	—	—	—	—	—	—	—	5.9 mg/dL Standard Error 1.56	3.0 mg/dL Standard Error 1.55	1.5 mg/dL Standard Error 1.56	—
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 26 (n=374, 380, 376)	—	—	—	—	—	—	—	—	8.0 mg/dL Standard Error 1.63	4.4 mg/dL Standard Error 1.61	3.9 mg/dL Standard Error 1.62	—
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 16 (n=374, 380, 376)	—	—	—	—	—	—	—	—	6.5 mg/dL Standard Error 1.52	1.2 mg/dL Standard Error 1.51	0.1 mg/dL Standard Error 1.51	—
Change From Baseline in Total Cholesterol Over Time (Grouped Analysis) Week 8 (n=374, 380, 376)	—	—	—	—	—	—	—	—	4.8 mg/dL Standard Error 1.42	-1.8 mg/dL Standard Error 1.41	-3.3 mg/dL Standard Error 1.42	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=117 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=112 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=112 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=111 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Total Cholesterol Levels	-2.3 mg/dL Standard Error 2.42	-10.2 mg/dL Standard Error 2.41	3.7 mg/dL Standard Error 2.42	-7.2 mg/dL Standard Error 2.38	-2.7 mg/dL Standard Error 2.41	-1.2 mg/dL Standard Error 2.43	-3.6 mg/dL Standard Error 2.43	-6.7 mg/dL Standard Error 2.47	1.3 mg/dL Standard Error 2.40	-3.8 mg/dL Standard Error 2.47	-3.7 mg/dL Standard Error 2.48	2.1 mg/dL Standard Error 2.47

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Total Cholesterol Levels	-2.3 mg/dL Standard Error 2.43	-4.1 mg/dL Standard Error 2.44	6.6 mg/dL Standard Error 2.48	0.1 mg/dL Standard Error 2.45	0.3 mg/dL Standard Error 2.47	0.3 mg/dL Standard Error 2.45	-3.1 mg/dL Standard Error 2.46	-6.2 mg/dL Standard Error 2.46	10.9 mg/dL Standard Error 2.46	-1.4 mg/dL Standard Error 2.50	-0.3 mg/dL Standard Error 2.48	7.3 mg/dL Standard Error 2.46

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Total Cholesterol Levels	1.9 mg/dL Standard Error 2.51	-0.2 mg/dL Standard Error 2.52	7.3 mg/dL Standard Error 2.56	0.3 mg/dL Standard Error 2.52	-1.0 mg/dL Standard Error 2.55	3.7 mg/dL Standard Error 2.53	1.7 mg/dL Standard Error 2.54	-3.9 mg/dL Standard Error 2.54	7.8 mg/dL Standard Error 2.54	0.4 mg/dL Standard Error 2.57	0.1 mg/dL Standard Error 2.56	8.7 mg/dL Standard Error 2.54

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Total Cholesterol Levels	-0.4 mg/dL Standard Error 2.59	3.2 mg/dL Standard Error 2.60	10.0 mg/dL Standard Error 2.65	0.9 mg/dL Standard Error 2.61	-1.2 mg/dL Standard Error 2.63	2.3 mg/dL Standard Error 2.61	2.9 mg/dL Standard Error 2.62	-1.8 mg/dL Standard Error 2.62	5.0 mg/dL Standard Error 2.62	-0.5 mg/dL Standard Error 2.66	-2.9 mg/dL Standard Error 2.65	7.2 mg/dL Standard Error 2.62

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Total Cholesterol Levels	4.0 mg/dL Standard Error 2.67	1.4 mg/dL Standard Error 2.68	7.0 mg/dL Standard Error 2.73	1.1 mg/dL Standard Error 2.68	3.4 mg/dL Standard Error 2.71	4.6 mg/dL Standard Error 2.69	4.0 mg/dL Standard Error 2.70	-0.3 mg/dL Standard Error 2.70	6.7 mg/dL Standard Error 2.70	1.8 mg/dL Standard Error 2.74	-1.9 mg/dL Standard Error 2.73	6.3 mg/dL Standard Error 2.70

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline total cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Total Cholesterol Levels	4.3 mg/dL Standard Error 2.78	3.5 mg/dL Standard Error 2.79	8.8 mg/dL Standard Error 2.84	2.8 mg/dL Standard Error 2.80	3.2 mg/dL Standard Error 2.83	9.5 mg/dL Standard Error 2.80	6.0 mg/dL Standard Error 2.81	5.1 mg/dL Standard Error 2.81	4.4 mg/dL Standard Error 2.82	2.2 mg/dL Standard Error 2.85	0.9 mg/dL Standard Error 2.84	5.8 mg/dL Standard Error 2.81

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in low-density lipoprotein cholesterol (LDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 4 (n=330, 336, 338)	—	—	—	—	—	—	—	—	3.1 mg/dL Standard Error 1.23	-0.5 mg/dL Standard Error 1.22	-1.9 mg/dL Standard Error 1.22	—
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 12 (n=365, 367, 366)	—	—	—	—	—	—	—	—	6.9 mg/dL Standard Error 1.29	3.3 mg/dL Standard Error 1.29	1.5 mg/dL Standard Error 1.29	—
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 8 (n=365, 365, 365)	—	—	—	—	—	—	—	—	5.9 mg/dL Standard Error 1.28	1.3 mg/dL Standard Error 1.28	0.1 mg/dL Standard Error 1.28	—
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 16 (n=365, 368, 366)	—	—	—	—	—	—	—	—	6.1 mg/dL Standard Error 1.29	3.3 mg/dL Standard Error 1.29	2.4 mg/dL Standard Error 1.29	—
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 20 (n=365, 368, 366)	—	—	—	—	—	—	—	—	6.9 mg/dL Standard Error 1.37	4.2 mg/dL Standard Error 1.36	3.0 mg/dL Standard Error 1.37	—
Change From Baseline in Low-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 26 (n=365, 368, 366)	—	—	—	—	—	—	—	—	7.4 mg/dL Standard Error 1.39	5.2 mg/dL Standard Error 1.39	5.6 mg/dL Standard Error 1.39	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=112 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=113 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=115 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=109 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=111 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=113 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=102 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=105 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=107 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Low-Density Lipoprotein Cholesterol	1.6 mg/dL Standard Error 2.12	-2.7 mg/dL Standard Error 2.11	3.2 mg/dL Standard Error 2.12	-2.8 mg/dL Standard Error 2.09	0.4 mg/dL Standard Error 2.10	3.4 mg/dL Standard Error 2.13	-0.3 mg/dL Standard Error 2.15	-3.4 mg/dL Standard Error 2.13	2.1 mg/dL Standard Error 2.11	-2.4 mg/dL Standard Error 2.22	1.4 mg/dL Standard Error 2.19	2.6 mg/dL Standard Error 2.16

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Low-Density Lipoprotein Cholesterol	-0.4 mg/dL Standard Error 2.21	1.0 mg/dL Standard Error 2.21	5.4 mg/dL Standard Error 2.24	2.4 mg/dL Standard Error 2.21	2.7 mg/dL Standard Error 2.24	4.8 mg/dL Standard Error 2.21	2.0 mg/dL Standard Error 2.24	-3.2 mg/dL Standard Error 2.20	9.4 mg/dL Standard Error 2.24	2.1 mg/dL Standard Error 2.30	3.4 mg/dL Standard Error 2.24	7.3 mg/dL Standard Error 2.21

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=115 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol	3.3 mg/dL Standard Error 2.21	3.8 mg/dL Standard Error 2.24	6.1 mg/dL Standard Error 2.26	1.9 mg/dL Standard Error 2.23	0.9 mg/dL Standard Error 2.25	5.7 mg/dL Standard Error 2.23	4.9 mg/dL Standard Error 2.26	-0.3 mg/dL Standard Error 2.22	6.5 mg/dL Standard Error 2.26	1.9 mg/dL Standard Error 2.30	3.7 mg/dL Standard Error 2.26	8.9 mg/dL Standard Error 2.24

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=116 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Low-Density Lipoprotein Cholesterol	2.9 mg/dL Standard Error 2.21	4.6 mg/dL Standard Error 2.23	7.1 mg/dL Standard Error 2.25	2.1 mg/dL Standard Error 2.23	0.8 mg/dL Standard Error 2.25	4.1 mg/dL Standard Error 2.22	4.9 mg/dL Standard Error 2.25	1.8 mg/dL Standard Error 2.21	4.2 mg/dL Standard Error 2.25	1.3 mg/dL Standard Error 2.29	0.9 mg/dL Standard Error 2.26	7.1 mg/dL Standard Error 2.23

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=116 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Low-Density Lipoprotein Cholesterol	4.3 mg/dL Standard Error 2.34	3.0 mg/dL Standard Error 2.37	6.6 mg/dL Standard Error 2.39	2.3 mg/dL Standard Error 2.36	4.1 mg/dL Standard Error 2.39	6.3 mg/dL Standard Error 2.36	6.1 mg/dL Standard Error 2.39	1.9 mg/dL Standard Error 2.35	6.9 mg/dL Standard Error 2.39	2.9 mg/dL Standard Error 2.43	1.9 mg/dL Standard Error 2.40	7.7 mg/dL Standard Error 2.37

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline LDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=120 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=116 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Low-Density Lipoprotein Cholesterol	3.7 mg/dL Standard Error 2.38	6.1 mg/dL Standard Error 2.41	6.2 mg/dL Standard Error 2.43	2.9 mg/dL Standard Error 2.40	3.0 mg/dL Standard Error 2.43	8.1 mg/dL Standard Error 2.40	9.1 mg/dL Standard Error 2.43	7.7 mg/dL Standard Error 2.39	3.6 mg/dL Standard Error 2.43	2.8 mg/dL Standard Error 2.47	3.6 mg/dL Standard Error 2.44	7.9 mg/dL Standard Error 2.41

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in high-density lipoprotein cholesterol (HDL-C) was assessed at Weeks 4, 8, 12, 16, 20 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 20 (n=374, 380, 376)	—	—	—	—	—	—	—	—	5.2 mg/dL Standard Error 0.40	5.7 mg/dL Standard Error 0.40	5.2 mg/dL Standard Error 0.40	—
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 4 (n=345, 353, 348)	—	—	—	—	—	—	—	—	3.0 mg/dL Standard Error 0.33	2.7 mg/dL Standard Error 0.33	3.4 mg/dL Standard Error 0.33	—
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 16 (n=374, 380, 376)	—	—	—	—	—	—	—	—	5.2 mg/dL Standard Error 0.39	5.2 mg/dL Standard Error 0.38	5.0 mg/dL Standard Error 0.38	—
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 8 (n=374, 380, 376)	—	—	—	—	—	—	—	—	4.0 mg/dL Standard Error 0.35	4.1 mg/dL Standard Error 0.34	4.6 mg/dL Standard Error 0.35	—
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 12 (n=374, 380, 376)	—	—	—	—	—	—	—	—	5.4 mg/dL Standard Error 0.37	5.3 mg/dL Standard Error 0.37	5.1 mg/dL Standard Error 0.37	—
Change From Baseline in High-Density Lipoprotein Cholesterol Over Time (Grouped Analysis) Week 26 (n=374, 380, 376)	—	—	—	—	—	—	—	—	5.1 mg/dL Standard Error 0.41	5.5 mg/dL Standard Error 0.41	5.0 mg/dL Standard Error 0.41	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=112 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=112 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=111 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in High-Density Lipoprotein Cholesterol	1.6 mg/dL Standard Error 0.58	1.6 mg/dL Standard Error 0.57	3.2 mg/dL Standard Error 0.57	2.3 mg/dL Standard Error 0.56	3.5 mg/dL Standard Error 0.57	3.3 mg/dL Standard Error 0.58	4.2 mg/dL Standard Error 0.58	5.1 mg/dL Standard Error 0.59	-0.4 mg/dL Standard Error 0.57	-0.6 mg/dL Standard Error 0.59	-0.5 mg/dL Standard Error 0.59	2.5 mg/dL Standard Error 0.59

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in High-Density Lipoprotein Cholesterol	2.3 mg/dL Standard Error 0.59	2.9 mg/dL Standard Error 0.60	4.8 mg/dL Standard Error 0.61	4.2 mg/dL Standard Error 0.60	4.6 mg/dL Standard Error 0.60	4.5 mg/dL Standard Error 0.60	5.7 mg/dL Standard Error 0.60	6.3 mg/dL Standard Error 0.60	-0.5 mg/dL Standard Error 0.60	-0.1 mg/dL Standard Error 0.61	0.6 mg/dL Standard Error 0.61	2.8 mg/dL Standard Error 0.60

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol	3.7 mg/dL Standard Error 0.63	3.7 mg/dL Standard Error 0.63	6.3 mg/dL Standard Error 0.64	5.8 mg/dL Standard Error 0.63	5.3 mg/dL Standard Error 0.64	6.1 mg/dL Standard Error 0.63	6.3 mg/dL Standard Error 0.64	6.4 mg/dL Standard Error 0.64	-0.2 mg/dL Standard Error 0.64	0.0 mg/dL Standard Error 0.65	0.3 mg/dL Standard Error 0.64	3.8 mg/dL Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in High-Density Lipoprotein Cholesterol	4.2 mg/dL Standard Error 0.66	4.0 mg/dL Standard Error 0.66	5.7 mg/dL Standard Error 0.67	5.5 mg/dL Standard Error 0.66	4.3 mg/dL Standard Error 0.67	5.9 mg/dL Standard Error 0.66	6.1 mg/dL Standard Error 0.67	6.7 mg/dL Standard Error 0.67	-0.3 mg/dL Standard Error 0.67	0.4 mg/dL Standard Error 0.68	0.7 mg/dL Standard Error 0.67	3.9 mg/dL Standard Error 0.67

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in High-Density Lipoprotein Cholesterol	4.3 mg/dL Standard Error 0.69	3.9 mg/dL Standard Error 0.69	5.9 mg/dL Standard Error 0.70	5.7 mg/dL Standard Error 0.69	5.3 mg/dL Standard Error 0.70	5.9 mg/dL Standard Error 0.70	7.1 mg/dL Standard Error 0.70	6.5 mg/dL Standard Error 0.70	0.6 mg/dL Standard Error 0.70	0.9 mg/dL Standard Error 0.71	0.5 mg/dL Standard Error 0.70	3.8 mg/dL Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HDL cholesterol as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in High-Density Lipoprotein Cholesterol	4.2 mg/dL Standard Error 0.70	4.1 mg/dL Standard Error 0.70	5.5 mg/dL Standard Error 0.71	6.0 mg/dL Standard Error 0.70	5.0 mg/dL Standard Error 0.71	6.1 mg/dL Standard Error 0.70	6.2 mg/dL Standard Error 0.71	6.0 mg/dL Standard Error 0.71	0.5 mg/dL Standard Error 0.71	0.6 mg/dL Standard Error 0.72	1.3 mg/dL Standard Error 0.71	3.8 mg/dL Standard Error 0.71

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in triglycerides was assessed at Weeks 4, 8, 12, 16, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 4 (n=345, 354, 348)	—	—	—	—	—	—	—	—	-31.5 mg/dL Standard Error 4.07	-38.9 mg/dL Standard Error 4.02	-48.0 mg/dL Standard Error 4.06	—
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 8 (n=374, 380, 376)	—	—	—	—	—	—	—	—	-34.7 mg/dL Standard Error 4.37	-44.4 mg/dL Standard Error 4.34	-47.9 mg/dL Standard Error 4.36	—
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 12 (n=374, 380, 376)	—	—	—	—	—	—	—	—	-34.5 mg/dL Standard Error 4.25	-47.5 mg/dL Standard Error 4.21	-49.4 mg/dL Standard Error 4.24	—
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 20 (n=374, 380, 376)	—	—	—	—	—	—	—	—	-34.9 mg/dL Standard Error 4.30	-43.6 mg/dL Standard Error 4.27	-42.7 mg/dL Standard Error 4.29	—
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 26 (n=374, 380, 376)	—	—	—	—	—	—	—	—	-29.6 mg/dL Standard Error 4.42	-41.4 mg/dL Standard Error 4.39	-40.7 mg/dL Standard Error 4.41	—
Change From Baseline in Triglycerides Over Time (Grouped Analysis) Week 16 (n=374, 380, 376)	—	—	—	—	—	—	—	—	-29.4 mg/dL Standard Error 4.43	-49.3 mg/dL Standard Error 4.39	-46.3 mg/dL Standard Error 4.42	—

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=117 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=112 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=112 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=111 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 4 in Triglyceride Levels	-35.8 mg/dL Standard Error 6.99	-51.1 mg/dL Standard Error 6.96	-26.7 mg/dL Standard Error 6.99	-42.2 mg/dL Standard Error 6.88	-44.4 mg/dL Standard Error 6.96	-47.1 mg/dL Standard Error 7.02	-39.2 mg/dL Standard Error 7.03	-49.1 mg/dL Standard Error 7.15	-2.4 mg/dL Standard Error 6.93	-2.2 mg/dL Standard Error 7.15	-25.0 mg/dL Standard Error 7.18	-21.5 mg/dL Standard Error 7.14

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=121 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Triglyceride Levels	-30.1 mg/dL Standard Error 7.47	-46.4 mg/dL Standard Error 7.50	-30.3 mg/dL Standard Error 7.62	-43.1 mg/dL Standard Error 7.51	-44.5 mg/dL Standard Error 7.60	-53.1 mg/dL Standard Error 7.53	-60.1 mg/dL Standard Error 7.57	-52.7 mg/dL Standard Error 7.56	26.3 mg/dL Standard Error 7.56	-16.4 mg/dL Standard Error 7.69	-23.0 mg/dL Standard Error 7.62	-20.5 mg/dL Standard Error 7.56

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Triglyceride Levels	-37.4 mg/dL Standard Error 7.26	-44.0 mg/dL Standard Error 7.29	-37.4 mg/dL Standard Error 7.40	-47.9 mg/dL Standard Error 7.29	-46.8 mg/dL Standard Error 7.38	-42.1 mg/dL Standard Error 7.31	-57.1 mg/dL Standard Error 7.35	-57.4 mg/dL Standard Error 7.35	18.9 mg/dL Standard Error 7.35	-4.3 mg/dL Standard Error 7.44	-18.1 mg/dL Standard Error 7.41	-24.1 mg/dL Standard Error 7.34

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 16 in Triglyceride Levels	-53.0 mg/dL Standard Error 7.57	-33.8 mg/dL Standard Error 7.60	-28.2 mg/dL Standard Error 7.72	-44.2 mg/dL Standard Error 7.60	-45.9 mg/dL Standard Error 7.69	-49.4 mg/dL Standard Error 7.63	-50.7 mg/dL Standard Error 7.66	-59.1 mg/dL Standard Error 7.66	10.6 mg/dL Standard Error 7.66	-7.5 mg/dL Standard Error 7.75	-26.8 mg/dL Standard Error 7.72	-10.5 mg/dL Standard Error 7.66

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Triglyceride Levels	-41.2 mg/dL Standard Error 7.35	-34.6 mg/dL Standard Error 7.38	-37.5 mg/dL Standard Error 7.50	-43.1 mg/dL Standard Error 7.39	-42.4 mg/dL Standard Error 7.47	-49.3 mg/dL Standard Error 7.41	-46.4 mg/dL Standard Error 7.44	-51.2 mg/dL Standard Error 7.44	5.7 mg/dL Standard Error 7.44	-7.0 mg/dL Standard Error 7.53	-23.7 mg/dL Standard Error 7.50	-18.0 mg/dL Standard Error 7.44

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=128 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=127 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=123 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=126 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=125 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=125 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=125 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Triglyceride Levels	-37.7 mg/dL Standard Error 7.56	-38.5 mg/dL Standard Error 7.59	-27.0 mg/dL Standard Error 7.71	-37.3 mg/dL Standard Error 7.59	-33.5 mg/dL Standard Error 7.68	-32.4 mg/dL Standard Error 7.62	-49.3 mg/dL Standard Error 7.65	-50.1 mg/dL Standard Error 7.65	3.7 mg/dL Standard Error 7.65	-1.1 mg/dL Standard Error 7.74	-15.2 mg/dL Standard Error 7.71	-29.5 mg/dL Standard Error 7.65

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in free fatty acids (FFA) was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) Week 12 (n=339, 356, 352)	—	—	—	—	—	—	—	—	-0.0707 mmol/L Standard Error 0.01483	-0.1306 mmol/L Standard Error 0.01447	-0.1273 mmol/L Standard Error 0.01455	—
Change From Baseline in Free Fatty Acids Over Time (Grouped Analysis) Week 26 (n=353, 368, 363)	—	—	—	—	—	—	—	—	-0.0676 mmol/L Standard Error 0.01050	-0.0945 mmol/L Standard Error 0.01029	-0.1144 mmol/L Standard Error 0.01036	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=116 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=116 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=115 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Free Fatty Acids	-0.1305 mmol/L Standard Error 0.02502	-0.1291 mmol/L Standard Error 0.02512	-0.0395 mmol/L Standard Error 0.02592	-0.1167 mmol/L Standard Error 0.02515	-0.1126 mmol/L Standard Error 0.02534	-0.0848 mmol/L Standard Error 0.02567	-0.1447 mmol/L Standard Error 0.02503	-0.1401 mmol/L Standard Error 0.02514	0.0067 mmol/L Standard Error 0.02493	-0.0149 mmol/L Standard Error 0.02535	-0.0769 mmol/L Standard Error 0.02535	-0.0879 mmol/L Standard Error 0.02547

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline free fatty acid as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Free Fatty Acids	-0.0752 mmol/L Standard Error 0.01772	-0.0972 mmol/L Standard Error 0.01793	-0.0737 mmol/L Standard Error 0.01817	-0.0956 mmol/L Standard Error 0.01788	-0.1232 mmol/L Standard Error 0.01801	-0.0730 mmol/L Standard Error 0.01816	-0.1125 mmol/L Standard Error 0.01787	-0.1228 mmol/L Standard Error 0.01787	-0.0387 mmol/L Standard Error 0.01788	-0.0427 mmol/L Standard Error 0.01802	-0.0386 mmol/L Standard Error 0.01787	-0.0561 mmol/L Standard Error 0.01825

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in plasminogen activator inhibitor-1 (PAI-1) was assessed at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) Week 12 (n=311, 333, 328)	—	—	—	—	—	—	—	—	-4.14 ng/mL Standard Error 1.970	-8.76 ng/mL Standard Error 1.900	-8.57 ng/mL Standard Error 1.914	—
Change From Baseline in Plasminogen Activator Inhibitor-1 Over Time (Grouped Analysis) Week 26 (n=341, 354, 348)	—	—	—	—	—	—	—	—	-4.56 ng/mL Standard Error 2.049	-2.69 ng/mL Standard Error 2.010	-9.25 ng/mL Standard Error 2.027	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=109 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=107 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=108 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=109 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=96 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=112 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=106 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=107 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=107 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=108 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Plasminogen Activator Inhibitor-1	-6.28 ng/mL Standard Error 3.260	-10.94 ng/mL Standard Error 3.320	-8.53 ng/mL Standard Error 3.353	-10.47 ng/mL Standard Error 3.336	-1.71 ng/mL Standard Error 3.321	1.85 ng/mL Standard Error 3.539	-9.13 ng/mL Standard Error 3.277	-12.63 ng/mL Standard Error 3.306	-4.55 ng/mL Standard Error 3.367	3.54 ng/mL Standard Error 3.350	-1.80 ng/mL Standard Error 3.353	-5.32 ng/mL Standard Error 3.340

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline PAI-1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=115 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=115 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=118 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=115 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Plasminogen Activator Inhibitor-1	-4.75 ng/mL Standard Error 3.465	-9.62 ng/mL Standard Error 3.510	-5.24 ng/mL Standard Error 3.495	1.89 ng/mL Standard Error 3.511	-6.66 ng/mL Standard Error 3.525	-3.02 ng/mL Standard Error 3.622	-5.22 ng/mL Standard Error 3.466	-11.48 ng/mL Standard Error 3.496	-3.00 ng/mL Standard Error 3.526	0.57 ng/mL Standard Error 3.540	-3.29 ng/mL Standard Error 3.481	-5.43 ng/mL Standard Error 3.529

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in high-sensitivity C-Reactive Protein (hsCRP) was assessed at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) Week 12 (n=346, 356, 355)	—	—	—	—	—	—	—	—	-2.0274 mg/L Standard Error 0.32717	-2.4653 mg/L Standard Error 0.32225	-1.9208 mg/L Standard Error 0.32253	—
Change From Baseline in High-sensitivity C-Reactive Protein Over Time (Grouped Analysis) Week 26 (n=359, 369, 363)	—	—	—	—	—	—	—	—	-0.8889 mg/L Standard Error 0.46384	-1.7716 mg/L Standard Error 0.45715	-0.9977 mg/L Standard Error 0.46059	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=118 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in High-sensitivity C-Reactive Protein	-2.2362 mg/L Standard Error 0.55706	-2.4217 mg/L Standard Error 0.55929	-2.7023 mg/L Standard Error 0.55971	-2.2143 mg/L Standard Error 0.55757	-1.0006 mg/L Standard Error 0.56412	-2.4212 mg/L Standard Error 0.57137	-2.9032 mg/L Standard Error 0.55979	-2.2978 mg/L Standard Error 0.55243	-1.1053 mg/L Standard Error 0.55528	-1.0730 mg/L Standard Error 0.56942	0.3516 mg/L Standard Error 0.55954	-0.9166 mg/L Standard Error 0.56902

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline hsCRP as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=124 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=123 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=121 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in High-sensitivity C-Reactive Protein	-1.2490 mg/L Standard Error 0.78817	-0.9438 mg/L Standard Error 0.79442	-1.0480 mg/L Standard Error 0.79805	-1.1725 mg/L Standard Error 0.79206	0.1697 mg/L Standard Error 0.80434	-1.8562 mg/L Standard Error 0.80771	-2.8933 mg/L Standard Error 0.79515	-2.2191 mg/L Standard Error 0.79450	-0.0550 mg/L Standard Error 0.79868	-0.6606 mg/L Standard Error 0.80145	0.2618 mg/L Standard Error 0.79488	0.2375 mg/L Standard Error 0.80439

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in adiponectin was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Adiponectin Over Time (Grouped Analysis) Week 12 (n=339, 357, 348)	—	—	—	—	—	—	—	—	6.03 μg/mL Standard Error 0.353	6.51 μg/mL Standard Error 0.344	6.51 μg/mL Standard Error 0.348	—
Change From Baseline in Adiponectin Over Time (Grouped Analysis) Week 26 (n=356, 369, 361)	—	—	—	—	—	—	—	—	5.98 μg/mL Standard Error 0.396	6.43 μg/mL Standard Error 0.388	6.46 μg/mL Standard Error 0.393	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=115 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Adiponectin	3.78 μg/mL Standard Error 0.591	2.91 μg/mL Standard Error 0.601	6.07 μg/mL Standard Error 0.617	6.31 μg/mL Standard Error 0.599	7.13 μg/mL Standard Error 0.609	8.47 μg/mL Standard Error 0.614	9.42 μg/mL Standard Error 0.598	9.46 μg/mL Standard Error 0.601	0.02 μg/mL Standard Error 0.593	0.44 μg/mL Standard Error 0.609	0.22 μg/mL Standard Error 0.606	3.54 μg/mL Standard Error 0.604

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline adiponectin as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=120 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=121 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Adiponectin	4.80 μg/mL Standard Error 0.664	2.93 μg/mL Standard Error 0.678	5.90 μg/mL Standard Error 0.687	6.30 μg/mL Standard Error 0.676	6.87 μg/mL Standard Error 0.684	8.75 μg/mL Standard Error 0.684	8.18 μg/mL Standard Error 0.678	9.59 μg/mL Standard Error 0.678	0.43 μg/mL Standard Error 0.676	0.48 μg/mL Standard Error 0.681	0.26 μg/mL Standard Error 0.678	3.30 μg/mL Standard Error 0.685

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 12, 20 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in body weight was assessed at Weeks 8, 12, 20 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Body Weight Over Time (Grouped Analysis) Week 12 (n=368, 374, 373)	—	—	—	—	—	—	—	—	0.56 kg Standard Error 0.125	0.57 kg Standard Error 0.124	0.82 kg Standard Error 0.124	—
Change From Baseline in Body Weight Over Time (Grouped Analysis) Week 20 (n=368, 374, 373)	—	—	—	—	—	—	—	—	1.21 kg Standard Error 0.152	1.45 kg Standard Error 0.151	1.46 kg Standard Error 0.151	—
Change From Baseline in Body Weight Over Time (Grouped Analysis) Week 26 (n=368, 374, 373)	—	—	—	—	—	—	—	—	1.49 kg Standard Error 0.168	1.81 kg Standard Error 0.167	1.87 kg Standard Error 0.167	—
Change From Baseline in Body Weight Over Time (Grouped Analysis) Week 8 (n=361, 372, 367)	—	—	—	—	—	—	—	—	0.45 kg Standard Error 0.103	0.34 kg Standard Error 0.101	0.63 kg Standard Error 0.102	—

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=126 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=122 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=123 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=119 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=121 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 8 in Body Weight	0.09 kg Standard Error 0.174	0.22 kg Standard Error 0.176	0.57 kg Standard Error 0.177	0.49 kg Standard Error 0.174	0.74 kg Standard Error 0.177	0.46 kg Standard Error 0.179	0.43 kg Standard Error 0.177	0.93 kg Standard Error 0.175	-0.13 kg Standard Error 0.176	-0.05 kg Standard Error 0.179	-0.45 kg Standard Error 0.178	0.32 kg Standard Error 0.177

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=123 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Body Weight	0.22 kg Standard Error 0.213	0.39 kg Standard Error 0.215	0.75 kg Standard Error 0.217	0.60 kg Standard Error 0.215	0.98 kg Standard Error 0.216	0.55 kg Standard Error 0.216	0.88 kg Standard Error 0.217	1.08 kg Standard Error 0.214	-0.46 kg Standard Error 0.216	-0.14 kg Standard Error 0.217	-0.56 kg Standard Error 0.216	0.39 kg Standard Error 0.217

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=123 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 20 in Body Weight	0.96 kg Standard Error 0.259	0.85 kg Standard Error 0.262	1.51 kg Standard Error 0.264	1.45 kg Standard Error 0.261	1.76 kg Standard Error 0.263	1.35 kg Standard Error 0.262	1.93 kg Standard Error 0.264	1.76 kg Standard Error 0.260	-0.55 kg Standard Error 0.263	-0.08 kg Standard Error 0.264	-0.48 kg Standard Error 0.263	0.76 kg Standard Error 0.264

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline weight as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=127 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=124 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=123 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=124 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=126 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=123 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=122 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=123 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=122 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Body Weight	1.25 kg Standard Error 0.287	1.27 kg Standard Error 0.290	1.88 kg Standard Error 0.292	1.89 kg Standard Error 0.289	2.10 kg Standard Error 0.291	1.65 kg Standard Error 0.290	2.30 kg Standard Error 0.292	2.25 kg Standard Error 0.288	-0.66 kg Standard Error 0.291	-0.02 kg Standard Error 0.292	-0.67 kg Standard Error 0.291	0.94 kg Standard Error 0.292

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

HOMA IR measures insulin resistance based on fasting glucose and insulin measurements:

HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.

A higher number indicates a greater insulin resistance. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) Week 12 (n=347, 344, 351)	—	—	—	—	—	—	—	—	-1.832 insulin resistance Standard Error 0.3122	-1.966 insulin resistance Standard Error 0.3136	-2.572 insulin resistance Standard Error 0.3104	—
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) (Grouped Analysis) Week 26 (n=348, 346, 352)	—	—	—	—	—	—	—	—	-1.571 insulin resistance Standard Error 0.3501	-2.209 insulin resistance Standard Error 0.3512	-1.711 insulin resistance Standard Error 0.3481	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements:

HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.

A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=117 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Calculated HOMA Insulin Resistance	-1.819 insulin resistance Standard Error 0.5376	-2.305 insulin resistance Standard Error 0.5352	-2.278 insulin resistance Standard Error 0.5446	-1.457 insulin resistance Standard Error 0.5473	-2.665 insulin resistance Standard Error 0.5400	-2.202 insulin resistance Standard Error 0.5447	-2.615 insulin resistance Standard Error 0.5446	-2.742 insulin resistance Standard Error 0.5377	0.337 insulin resistance Standard Error 0.5333	0.063 insulin resistance Standard Error 0.5375	0.041 insulin resistance Standard Error 0.5270	-1.012 insulin resistance Standard Error 0.5330

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The Homeostasis Model Assessment of insulin resistance (HOMA IR) measures insulin resistance based on fasting glucose and insulin measurements:

HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5.

A higher number indicates a greater degree of insulin resistance. Least Squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and HOMA-IR as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=115 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Calculated HOMA Insulin Resistance	-2.300 insulin resistance Standard Error 0.5986	-0.223 insulin resistance Standard Error 0.5985	-2.061 insulin resistance Standard Error 0.6089	-1.871 insulin resistance Standard Error 0.6147	-2.056 insulin resistance Standard Error 0.6064	-1.789 insulin resistance Standard Error 0.6117	-2.456 insulin resistance Standard Error 0.6116	-2.854 insulin resistance Standard Error 0.6038	0.464 insulin resistance Standard Error 0.5988	0.311 insulin resistance Standard Error 0.6036	-0.179 insulin resistance Standard Error 0.5918	-0.864 insulin resistance Standard Error 0.5985

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B).

HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) Week 12 (n=347, 344, 350)	—	—	—	—	—	—	—	—	2.591 percentage beta cell function Standard Error 3.7892	23.799 percentage beta cell function Standard Error 3.8017	19.477 percentage beta cell function Standard Error 3.7685	—
Change From Baseline in Homeostatic Model Assessment Beta Cell Function (Grouped Analysis) Week 26 (n=348, 346, 351)	—	—	—	—	—	—	—	—	5.060 percentage beta cell function Standard Error 3.0460	18.173 percentage beta cell function Standard Error 3.0522	22.182 percentage beta cell function Standard Error 3.0297	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.

HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=117 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=118 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Calculated HOMA Beta-cell Function	30.346 percentage beta cell function Standard Error 6.5157	19.887 percentage beta cell function Standard Error 6.4916	1.118 percentage beta cell function Standard Error 6.6030	21.045 percentage beta cell function Standard Error 6.6358	19.935 percentage beta cell function Standard Error 6.5444	4.023 percentage beta cell function Standard Error 6.6240	19.938 percentage beta cell function Standard Error 6.6025	18.541 percentage beta cell function Standard Error 6.5456	-3.027 percentage beta cell function Standard Error 6.4915	16.304 percentage beta cell function Standard Error 6.5165	22.996 percentage beta cell function Standard Error 6.3854	2.565 percentage beta cell function Standard Error 6.4614

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.

HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline HOMA beta cell function as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=115 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=118 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=122 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Calculated HOMA Beta-cell Function	10.977 percentage beta cell function Standard Error 5.2010	19.320 percentage beta cell function Standard Error 5.2044	8.983 percentage beta cell function Standard Error 5.2921	22.474 percentage beta cell function Standard Error 5.3423	23.475 percentage beta cell function Standard Error 5.2687	3.427 percentage beta cell function Standard Error 5.3327	21.068 percentage beta cell function Standard Error 5.3154	23.752 percentage beta cell function Standard Error 5.2696	-0.924 percentage beta cell function Standard Error 5.2260	11.812 percentage beta cell function Standard Error 5.2462	17.814 percentage beta cell function Standard Error 5.1407	2.770 percentage beta cell function Standard Error 5.2018

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in Apolipoprotein A1 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) Week 12 (n=339, 354, 346)	—	—	—	—	—	—	—	—	1.4 mg/dL Standard Error 1.00	0.2 mg/dL Standard Error 0.98	0.3 mg/dL Standard Error 0.99	—
Change From Baseline in Apolipoprotein A1 Over Time (Grouped Analysis) Week 26 (n=354, 367, 356)	—	—	—	—	—	—	—	—	-1.6 mg/dL Standard Error 1.09	-1.5 mg/dL Standard Error 1.08	-2.8 mg/dL Standard Error 1.09	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=117 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=112 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Apolipoprotein A1	-1.3 mg/dL Standard Error 1.69	1.7 mg/dL Standard Error 1.72	3.5 mg/dL Standard Error 1.72	0.7 mg/dL Standard Error 1.69	0.4 mg/dL Standard Error 1.69	-0.1 mg/dL Standard Error 1.74	1.1 mg/dL Standard Error 1.71	-1.2 mg/dL Standard Error 1.72	-1.9 mg/dL Standard Error 1.70	-4.4 mg/dL Standard Error 1.73	-3.0 mg/dL Standard Error 1.74	0.8 mg/dL Standard Error 1.73

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A1 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=118 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Apolipoprotein A1	-3.5 mg/dL Standard Error 1.84	-2.9 mg/dL Standard Error 1.91	-0.2 mg/dL Standard Error 1.89	-0.1 mg/dL Standard Error 1.86	-3.2 mg/dL Standard Error 1.87	-1.4 mg/dL Standard Error 1.89	-1.0 mg/dL Standard Error 1.88	-2.2 mg/dL Standard Error 1.89	-4.9 mg/dL Standard Error 1.88	-3.0 mg/dL Standard Error 1.90	-4.2 mg/dL Standard Error 1.89	-3.3 mg/dL Standard Error 1.90

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in Apolipoprotein A2 was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) Week 12 (n=339, 354, 345)	—	—	—	—	—	—	—	—	3.1 mg/dL Standard Error 0.26	2.5 mg/dL Standard Error 0.26	2.3 mg/dL Standard Error 0.26	—
Change From Baseline in Apolipoprotein A2 Over Time (Grouped Analysis) Week 26 (n=354, 367, 355)	—	—	—	—	—	—	—	—	2.4 mg/dL Standard Error 0.28	2.1 mg/dL Standard Error 0.27	1.8 mg/dL Standard Error 0.28	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=112 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=117 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=112 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Apolipoprotein A2	1.4 mg/dL Standard Error 0.44	1.9 mg/dL Standard Error 0.45	3.7 mg/dL Standard Error 0.45	2.5 mg/dL Standard Error 0.44	1.8 mg/dL Standard Error 0.44	3.0 mg/dL Standard Error 0.45	3.7 mg/dL Standard Error 0.45	3.2 mg/dL Standard Error 0.45	0.4 mg/dL Standard Error 0.44	0.1 mg/dL Standard Error 0.45	0.4 mg/dL Standard Error 0.45	2.4 mg/dL Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein A2 as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=118 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Apolipoprotein A2	1.2 mg/dL Standard Error 0.47	1.0 mg/dL Standard Error 0.48	2.7 mg/dL Standard Error 0.48	2.1 mg/dL Standard Error 0.47	1.6 mg/dL Standard Error 0.47	2.8 mg/dL Standard Error 0.48	3.1 mg/dL Standard Error 0.47	2.7 mg/dL Standard Error 0.48	0.1 mg/dL Standard Error 0.47	0.2 mg/dL Standard Error 0.48	0.4 mg/dL Standard Error 0.48	1.9 mg/dL Standard Error 0.48

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in Apolipoprotein B was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) Week 12 (n=338, 354, 346)	—	—	—	—	—	—	—	—	-3.0 mg/dL Standard Error 1.09	-7.9 mg/dL Standard Error 1.06	-10.0 mg/dL Standard Error 1.07	—
Change From Baseline in Apolipoprotein B Over Time (Grouped Analysis) Week 26 (n=354, 367, 356)	—	—	—	—	—	—	—	—	-2.8 mg/dL Standard Error 1.16	-6.4 mg/dL Standard Error 1.14	-6.4 mg/dL Standard Error 1.15	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=114 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=117 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=112 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Apolipoprotein B	-7.2 mg/dL Standard Error 1.83	-6.1 mg/dL Standard Error 1.87	-2.1 mg/dL Standard Error 1.88	-8.4 mg/dL Standard Error 1.83	-12.2 mg/dL Standard Error 1.84	-6.6 mg/dL Standard Error 1.90	-8.0 mg/dL Standard Error 1.86	-11.7 mg/dL Standard Error 1.87	5.0 mg/dL Standard Error 1.85	-2.3 mg/dL Standard Error 1.87	-3.6 mg/dL Standard Error 1.89	-0.3 mg/dL Standard Error 1.88

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein B as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=122 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=118 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=119 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=118 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Apolipoprotein B	-6.0 mg/dL Standard Error 1.95	-4.8 mg/dL Standard Error 2.02	-3.2 mg/dL Standard Error 2.00	-7.2 mg/dL Standard Error 1.97	-8.8 mg/dL Standard Error 1.98	-3.6 mg/dL Standard Error 2.00	-6.1 mg/dL Standard Error 1.99	-5.5 mg/dL Standard Error 2.00	0.6 mg/dL Standard Error 1.99	-0.6 mg/dL Standard Error 2.00	-3.7 mg/dL Standard Error 2.00	-1.5 mg/dL Standard Error 2.01

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Change from Baseline in apolipoprotein C-III was assessed at Weeks 12 and 26. This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) Week 12 (n=337, 352, 345)	—	—	—	—	—	—	—	—	-0.6 mg/dL Standard Error 0.17	-1.2 mg/dL Standard Error 0.16	-1.3 mg/dL Standard Error 0.17	—
Change From Baseline in Apolipoprotein C-III Over Time (Grouped Analysis) Week 26 (n=353, 366, 355)	—	—	—	—	—	—	—	—	-0.1 mg/dL Standard Error 0.19	-0.6 mg/dL Standard Error 0.19	-0.6 mg/dL Standard Error 0.19	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=114 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=111 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=116 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=113 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=117 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=114 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=112 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Apolipoprotein C-III	-1.0 mg/dL Standard Error 0.28	-1.4 mg/dL Standard Error 0.29	-0.3 mg/dL Standard Error 0.29	-1.0 mg/dL Standard Error 0.28	-1.3 mg/dL Standard Error 0.28	-1.1 mg/dL Standard Error 0.29	-1.4 mg/dL Standard Error 0.29	-1.2 mg/dL Standard Error 0.29	0.7 mg/dL Standard Error 0.28	-0.4 mg/dL Standard Error 0.29	-0.7 mg/dL Standard Error 0.29	-0.3 mg/dL Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline apolipoprotein C-III as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=125 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=119 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=118 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=120 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=118 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=119 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=117 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Apolipoprotein C-III	-0.6 mg/dL Standard Error 0.32	-0.7 mg/dL Standard Error 0.33	0.2 mg/dL Standard Error 0.33	-0.4 mg/dL Standard Error 0.32	-0.6 mg/dL Standard Error 0.32	0.0 mg/dL Standard Error 0.33	-0.7 mg/dL Standard Error 0.33	-0.5 mg/dL Standard Error 0.33	0.4 mg/dL Standard Error 0.33	0.5 mg/dL Standard Error 0.33	-0.7 mg/dL Standard Error 0.33	-0.4 mg/dL Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

Nuclear Magnetic Resonance (NMR) lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-19.6 mg/dL Standard Error 3.92	-28.8 mg/dL Standard Error 3.85	-31.5 mg/dL Standard Error 3.86	—
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides Over Time (Grouped Analysis) Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-11.5 mg/dL Standard Error 4.30	-25.4 mg/dL Standard Error 4.23	-22.9 mg/dL Standard Error 4.24	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 12.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in NMR Lipid Fractionation Total Triglycerides	-21.8 mg/dL Standard Error 6.70	-27.2 mg/dL Standard Error 6.61	-18.3 mg/dL Standard Error 6.82	-29.8 mg/dL Standard Error 6.73	-31.6 mg/dL Standard Error 6.82	-27.9 mg/dL Standard Error 6.85	-35.1 mg/dL Standard Error 6.59	-36.0 mg/dL Standard Error 6.64	20.6 mg/dL Standard Error 6.56	-4.9 mg/dL Standard Error 6.73	-7.8 mg/dL Standard Error 6.70	-12.9 mg/dL Standard Error 6.72

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

NMR lipid fractionation was used to assess the change from Baseline in total triglyceride levels at Week 26.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR total triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in NMR Lipid Fractionation Total Triglycerides	-20.4 mg/dL Standard Error 7.32	-23.1 mg/dL Standard Error 7.32	-6.9 mg/dL Standard Error 7.44	-23.5 mg/dL Standard Error 7.38	-19.7 mg/dL Standard Error 7.44	-8.6 mg/dL Standard Error 7.44	-32.1 mg/dL Standard Error 7.29	-25.8 mg/dL Standard Error 7.29	12.4 mg/dL Standard Error 7.26	7.3 mg/dL Standard Error 7.42	-6.8 mg/dL Standard Error 7.32	-18.9 mg/dL Standard Error 7.44

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) Large Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-1.61 nmol/L Standard Error 0.289	-2.20 nmol/L Standard Error 0.283	-2.17 nmol/L Standard Error 0.284	—
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) Total Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-1.85 nmol/L Standard Error 1.803	-6.40 nmol/L Standard Error 1.770	-7.26 nmol/L Standard Error 1.775	—
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) Total Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-1.05 nmol/L Standard Error 1.999	-1.87 nmol/L Standard Error 1.970	-1.31 nmol/L Standard Error 1.975	—
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles Over Time (Grouped Analysis) Large Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-1.05 nmol/L Standard Error 0.342	-2.25 nmol/L Standard Error 0.337	-1.98 nmol/L Standard Error 0.337	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in VLDL / Chylomicron Particles Total Particles	-3.46 nmol/L Standard Error 3.077	-5.57 nmol/L Standard Error 3.037	0.45 nmol/L Standard Error 3.135	-7.82 nmol/L Standard Error 3.092	-6.54 nmol/L Standard Error 3.132	-8.58 nmol/L Standard Error 3.147	-7.99 nmol/L Standard Error 3.027	-9.76 nmol/L Standard Error 3.051	5.82 nmol/L Standard Error 3.013	-1.59 nmol/L Standard Error 3.092	-5.32 nmol/L Standard Error 3.077	2.52 nmol/L Standard Error 3.089
Change From Baseline to Week 12 in VLDL / Chylomicron Particles Large Particles	-1.63 nmol/L Standard Error 0.493	-1.81 nmol/L Standard Error 0.486	-1.69 nmol/L Standard Error 0.502	-2.19 nmol/L Standard Error 0.495	-2.29 nmol/L Standard Error 0.501	-1.97 nmol/L Standard Error 0.504	-2.81 nmol/L Standard Error 0.484	-2.45 nmol/L Standard Error 0.489	1.12 nmol/L Standard Error 0.482	-0.42 nmol/L Standard Error 0.495	-0.27 nmol/L Standard Error 0.493	-1.20 nmol/L Standard Error 0.495

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total VLDL/chylomicron particles and large VLDL/chylomicron particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in VLDL / Chylomicron Particles Large Particles	-1.71 nmol/L Standard Error 0.582	-1.80 nmol/L Standard Error 0.582	-0.90 nmol/L Standard Error 0.592	-2.24 nmol/L Standard Error 0.587	-1.79 nmol/L Standard Error 0.592	-0.67 nmol/L Standard Error 0.592	-2.80 nmol/L Standard Error 0.580	-2.36 nmol/L Standard Error 0.580	1.31 nmol/L Standard Error 0.577	0.94 nmol/L Standard Error 0.589	-0.14 nmol/L Standard Error 0.582	-1.56 nmol/L Standard Error 0.592
Change From Baseline to Week 26 in VLDL / Chylomicron Particles Total Particles	-3.31 nmol/L Standard Error 3.405	-5.15 nmol/L Standard Error 3.405	3.68 nmol/L Standard Error 3.464	-0.59 nmol/L Standard Error 3.436	-0.35 nmol/L Standard Error 3.463	-3.83 nmol/L Standard Error 3.463	-1.70 nmol/L Standard Error 3.394	1.56 nmol/L Standard Error 3.392	2.80 nmol/L Standard Error 3.379	0.59 nmol/L Standard Error 3.450	-5.79 nmol/L Standard Error 3.405	-2.99 nmol/L Standard Error 3.462

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of VLDL/chylomicron triglycerides was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-20.4 mg/dL Standard Error 3.90	-28.5 mg/dL Standard Error 3.83	-30.3 mg/dL Standard Error 3.84	—
Change From Baseline in VLDL / Chylomicron Triglycerides Over Time (Grouped Analysis) Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-13.0 mg/dL Standard Error 4.28	-25.4 mg/dL Standard Error 4.22	-23.0 mg/dL Standard Error 4.23	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in VLDL / Chylomicron Triglycerides	-21.1 mg/dL Standard Error 6.65	-26.5 mg/dL Standard Error 6.56	-19.1 mg/dL Standard Error 6.78	-29.5 mg/dL Standard Error 6.69	-30.1 mg/dL Standard Error 6.77	-28.4 mg/dL Standard Error 6.80	-35.5 mg/dL Standard Error 6.55	-34.8 mg/dL Standard Error 6.60	19.9 mg/dL Standard Error 6.51	-3.5 mg/dL Standard Error 6.69	-6.4 mg/dL Standard Error 6.65	-14.2 mg/dL Standard Error 6.68

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in VLDL/chylomicron triglyceride levels was assessed by NMR lipid fractionation. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL/chylomicron triglycerides as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in VLDL / Chylomicron Triglycerides	-20.4 mg/dL Standard Error 7.29	-23.8 mg/dL Standard Error 7.29	-8.2 mg/dL Standard Error 7.41	-23.5 mg/dL Standard Error 7.35	-18.9 mg/dL Standard Error 7.41	-10.4 mg/dL Standard Error 7.41	-32.3 mg/dL Standard Error 7.26	-26.2 mg/dL Standard Error 7.26	11.9 mg/dL Standard Error 7.23	8.3 mg/dL Standard Error 7.39	-7.0 mg/dL Standard Error 7.29	-20.4 mg/dL Standard Error 7.41

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in VLDL Particles Over Time (Grouped Analysis) Medium Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-4.44 nmol/L Standard Error 1.174	-5.36 nmol/L Standard Error 1.152	-7.30 nmol/L Standard Error 1.155	—
Change From Baseline in VLDL Particles Over Time (Grouped Analysis) Medium Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-2.28 nmol/L Standard Error 1.346	-3.02 nmol/L Standard Error 1.326	-4.88 nmol/L Standard Error 1.329	—
Change From Baseline in VLDL Particles Over Time (Grouped Analysis) Small Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	4.16 nmol/L Standard Error 1.053	1.33 nmol/L Standard Error 1.033	1.91 nmol/L Standard Error 1.035	—
Change From Baseline in VLDL Particles Over Time (Grouped Analysis) Small Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	2.30 nmol/L Standard Error 1.084	3.55 nmol/L Standard Error 1.067	5.22 nmol/L Standard Error 1.070	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in VLDL Particles Small Particles	1.16 nmol/L Standard Error 1.796	2.60 nmol/L Standard Error 1.772	4.39 nmol/L Standard Error 1.829	1.15 nmol/L Standard Error 1.806	2.51 nmol/L Standard Error 1.828	2.22 nmol/L Standard Error 1.839	1.80 nmol/L Standard Error 1.765	0.73 nmol/L Standard Error 1.780	2.76 nmol/L Standard Error 1.758	0.39 nmol/L Standard Error 1.804	-2.30 nmol/L Standard Error 1.797	5.99 nmol/L Standard Error 1.803
Change From Baseline to Week 12 in VLDL Particles Medium Particles	-3.16 nmol/L Standard Error 2.004	-6.51 nmol/L Standard Error 1.977	-2.59 nmol/L Standard Error 2.041	-6.70 nmol/L Standard Error 2.013	-7.05 nmol/L Standard Error 2.039	-8.64 nmol/L Standard Error 2.048	-6.38 nmol/L Standard Error 1.971	-8.50 nmol/L Standard Error 1.987	2.13 nmol/L Standard Error 1.962	-1.13 nmol/L Standard Error 2.014	-2.88 nmol/L Standard Error 2.003	-2.25 nmol/L Standard Error 2.011

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of medium VLDL particles and small VLDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR VLDL particles as continuous covariates

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in VLDL Particles Medium Particles	-1.78 nmol/L Standard Error 2.293	-5.42 nmol/L Standard Error 2.292	0.28 nmol/L Standard Error 2.332	-2.17 nmol/L Standard Error 2.313	-4.38 nmol/L Standard Error 2.331	-2.70 nmol/L Standard Error 2.331	-5.09 nmol/L Standard Error 2.285	-4.83 nmol/L Standard Error 2.284	1.54 nmol/L Standard Error 2.275	0.85 nmol/L Standard Error 2.324	-2.94 nmol/L Standard Error 2.292	-4.43 nmol/L Standard Error 2.331
Change From Baseline to Week 26 in VLDL Particles Small Particles	-0.19 nmol/L Standard Error 1.845	1.90 nmol/L Standard Error 1.845	4.16 nmol/L Standard Error 1.877	4.07 nmol/L Standard Error 1.863	5.45 nmol/L Standard Error 1.876	-0.08 nmol/L Standard Error 1.878	6.77 nmol/L Standard Error 1.837	8.33 nmol/L Standard Error 1.837	0.26 nmol/L Standard Error 1.831	-0.87 nmol/L Standard Error 1.868	-2.91 nmol/L Standard Error 1.846	2.83 nmol/L Standard Error 1.876

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) Week 26 (n=348, 358, 357)	—	—	—	—	—	—	—	—	-2.49 nm Standard Error 0.406	-3.67 nm Standard Error 0.400	-3.26 nm Standard Error 0.400	—
Change From Baseline in Mean VLDL Particle Size Over Time (Grouped Analysis) Week 12 (n=332, 344, 343)	—	—	—	—	—	—	—	—	-2.77 nm Standard Error 0.398	-2.98 nm Standard Error 0.390	-3.02 nm Standard Error 0.391	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Mean VLDL Particle Size	-2.10 nm Standard Error 0.681	-2.56 nm Standard Error 0.669	-3.16 nm Standard Error 0.690	-2.88 nm Standard Error 0.681	-2.49 nm Standard Error 0.690	-2.37 nm Standard Error 0.694	-4.00 nm Standard Error 0.666	-4.03 nm Standard Error 0.672	0.65 nm Standard Error 0.664	0.12 nm Standard Error 0.681	-0.18 nm Standard Error 0.678	-2.81 nm Standard Error 0.681

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean VLDL particle size was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean VLDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=119 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Mean VLDL Particle Size	-2.66 nm Standard Error 0.694	-2.36 nm Standard Error 0.691	-2.88 nm Standard Error 0.703	-3.69 nm Standard Error 0.697	-3.30 nm Standard Error 0.702	-1.60 nm Standard Error 0.703	-4.65 nm Standard Error 0.688	-4.12 nm Standard Error 0.688	0.26 nm Standard Error 0.685	0.52 nm Standard Error 0.700	0.35 nm Standard Error 0.691	-2.99 nm Standard Error 0.703

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	2.8 nmol/L Standard Error 2.16	-4.2 nmol/L Standard Error 2.13	-1.5 nmol/L Standard Error 2.13	—
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles Over Time (Grouped Analysis) Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	0.4 nmol/L Standard Error 2.16	-3.9 nmol/L Standard Error 2.12	-5.7 nmol/L Standard Error 2.12	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in IDL Particles	-6.0 nmol/L Standard Error 3.68	-2.3 nmol/L Standard Error 3.64	-2.2 nmol/L Standard Error 3.75	-6.3 nmol/L Standard Error 3.70	-8.1 nmol/L Standard Error 3.75	-1.5 nmol/L Standard Error 3.76	0.7 nmol/L Standard Error 3.62	-6.5 nmol/L Standard Error 3.65	1.6 nmol/L Standard Error 3.60	-11.1 nmol/L Standard Error 3.70	-6.0 nmol/L Standard Error 3.68	5.1 nmol/L Standard Error 3.70

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of IDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR IDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in IDL Particles	-2.4 nmol/L Standard Error 3.67	0.0 nmol/L Standard Error 3.68	3.0 nmol/L Standard Error 3.74	-5.0 nmol/L Standard Error 3.71	-5.5 nmol/L Standard Error 3.74	0.1 nmol/L Standard Error 3.74	-5.0 nmol/L Standard Error 3.66	1.0 nmol/L Standard Error 3.66	5.1 nmol/L Standard Error 3.65	-7.3 nmol/L Standard Error 3.73	-3.2 nmol/L Standard Error 3.68	5.2 nmol/L Standard Error 3.74

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Medium-Small Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-34.3 nmol/L Standard Error 4.22	-44.9 nmol/L Standard Error 4.16	-49.6 nmol/L Standard Error 4.17	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Total Small Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-191.4 nmol/L Standard Error 20.32	-287.5 nmol/L Standard Error 19.94	-331.4 nmol/L Standard Error 20.00	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Total Small Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-178.1 nmol/L Standard Error 21.13	-235.0 nmol/L Standard Error 20.81	-285.9 nmol/L Standard Error 20.87	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Large Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	95.8 nmol/L Standard Error 11.11	93.9 nmol/L Standard Error 10.93	106.1 nmol/L Standard Error 10.96	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Medium-Small Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-36.6 nmol/L Standard Error 4.11	-55.3 nmol/L Standard Error 4.03	-60.1 nmol/L Standard Error 4.04	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Very Small Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-154.6 nmol/L Standard Error 16.53	-232.3 nmol/L Standard Error 16.23	-271.3 nmol/L Standard Error 16.27	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Very Small Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-143.6 nmol/L Standard Error 17.23	-190.3 nmol/L Standard Error 16.97	-236.2 nmol/L Standard Error 17.02	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Total Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-104.1 nmol/L Standard Error 17.46	-180.5 nmol/L Standard Error 17.13	-236.8 nmol/L Standard Error 17.18	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Total Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-78.2 nmol/L Standard Error 17.83	-146.2 nmol/L Standard Error 17.55	-182.9 nmol/L Standard Error 17.60	—
Change From Baseline in Low Density Lipoprotein (LDL) Particles Over Time (Grouped Analysis) Large Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	85.5 nmol/L Standard Error 10.02	111.6 nmol/L Standard Error 9.83	102.3 nmol/L Standard Error 9.85	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in LDL Particles Total Particles	-143.5 nmol/L Standard Error 29.79	-175.6 nmol/L Standard Error 29.43	-96.2 nmol/L Standard Error 30.37	-195.8 nmol/L Standard Error 29.93	-248.8 nmol/L Standard Error 30.31	-167.0 nmol/L Standard Error 30.46	-202.2 nmol/L Standard Error 29.27	-285.8 nmol/L Standard Error 29.52	52.0 nmol/L Standard Error 29.17	-39.1 nmol/L Standard Error 29.92	-69.9 nmol/L Standard Error 29.80	-48.8 nmol/L Standard Error 29.91
Change From Baseline to Week 12 in LDL Particles Total Small Particles	-211.0 nmol/L Standard Error 34.69	-256.3 nmol/L Standard Error 34.26	-184.1 nmol/L Standard Error 35.32	-313.7 nmol/L Standard Error 34.85	-345.4 nmol/L Standard Error 35.29	-280.4 nmol/L Standard Error 35.46	-337.9 nmol/L Standard Error 34.08	-392.7 nmol/L Standard Error 34.38	45.1 nmol/L Standard Error 33.98	-52.0 nmol/L Standard Error 34.83	-56.5 nmol/L Standard Error 34.70	-109.9 nmol/L Standard Error 34.83
Change From Baseline to Week 12 in LDL Particles Very Small Particles	-170.3 nmol/L Standard Error 28.22	-207.6 nmol/L Standard Error 27.87	-149.8 nmol/L Standard Error 28.74	-255.7 nmol/L Standard Error 28.36	-281.5 nmol/L Standard Error 28.72	-225.0 nmol/L Standard Error 28.85	-271.0 nmol/L Standard Error 27.73	-325.0 nmol/L Standard Error 27.97	36.4 nmol/L Standard Error 27.65	-44.1 nmol/L Standard Error 28.34	-51.9 nmol/L Standard Error 28.23	-89.2 nmol/L Standard Error 28.33
Change From Baseline to Week 12 in LDL Particles Medium-Small Particles	-41.1 nmol/L Standard Error 7.01	-48.0 nmol/L Standard Error 6.93	-34.4 nmol/L Standard Error 7.14	-58.2 nmol/L Standard Error 7.05	-64.1 nmol/L Standard Error 7.14	-55.4 nmol/L Standard Error 7.17	-66.8 nmol/L Standard Error 6.89	-68.2 nmol/L Standard Error 6.96	9.4 nmol/L Standard Error 6.87	-7.7 nmol/L Standard Error 7.04	-5.1 nmol/L Standard Error 7.02	-20.3 nmol/L Standard Error 7.04
Change From Baseline to Week 12 in LDL Particles Large Particles	73.8 nmol/L Standard Error 17.08	85.7 nmol/L Standard Error 16.86	83.9 nmol/L Standard Error 17.43	126.2 nmol/L Standard Error 17.18	105.7 nmol/L Standard Error 17.39	116.9 nmol/L Standard Error 17.48	135.2 nmol/L Standard Error 16.79	116.1 nmol/L Standard Error 16.95	4.7 nmol/L Standard Error 16.74	21.1 nmol/L Standard Error 17.16	-8.0 nmol/L Standard Error 17.09	56.2 nmol/L Standard Error 17.15

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium-small, total small and very small LDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR LDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in LDL Particles Total Particles	-115.1 nmol/L Standard Error 30.35	-119.4 nmol/L Standard Error 30.37	-68.6 nmol/L Standard Error 30.90	-158.9 nmol/L Standard Error 30.62	-209.4 nmol/L Standard Error 30.85	-119.7 nmol/L Standard Error 30.87	-164.6 nmol/L Standard Error 30.22	-219.9 nmol/L Standard Error 30.21	15.0 nmol/L Standard Error 30.11	-14.5 nmol/L Standard Error 30.73	-30.8 nmol/L Standard Error 30.36	-46.3 nmol/L Standard Error 30.86
Change From Baseline to Week 26 in LDL Particles Large Particles	63.2 nmol/L Standard Error 18.90	93.1 nmol/L Standard Error 18.90	79.3 nmol/L Standard Error 19.27	96.6 nmol/L Standard Error 19.09	102.7 nmol/L Standard Error 19.22	137.7 nmol/L Standard Error 19.23	121.9 nmol/L Standard Error 18.83	122.7 nmol/L Standard Error 18.83	-23.8 nmol/L Standard Error 18.77	-12.3 nmol/L Standard Error 19.14	15.3 nmol/L Standard Error 18.91	70.5 nmol/L Standard Error 19.22
Change From Baseline to Week 26 in LDL Particles Medium-Small Particles	-29.9 nmol/L Standard Error 7.19	-36.2 nmol/L Standard Error 7.20	-30.0 nmol/L Standard Error 7.32	-47.4 nmol/L Standard Error 7.26	-55.0 nmol/L Standard Error 7.31	-47.1 nmol/L Standard Error 7.31	-57.6 nmol/L Standard Error 7.16	-57.8 nmol/L Standard Error 7.17	9.1 nmol/L Standard Error 7.14	0.0 nmol/L Standard Error 7.28	-6.9 nmol/L Standard Error 7.20	-25.8 nmol/L Standard Error 7.31
Change From Baseline to Week 26 in LDL Particles Total Small Particles	-175.1 nmol/L Standard Error 35.99	-211.5 nmol/L Standard Error 36.01	-154.9 nmol/L Standard Error 36.60	-248.7 nmol/L Standard Error 36.31	-304.9 nmol/L Standard Error 36.58	-256.9 nmol/L Standard Error 36.58	-281.1 nmol/L Standard Error 35.82	-341.3 nmol/L Standard Error 35.82	32.4 nmol/L Standard Error 35.72	2.2 nmol/L Standard Error 36.44	-42.9 nmol/L Standard Error 36.00	-122.5 nmol/L Standard Error 36.59
Change From Baseline to Week 26 in LDL Particles Very Small Particles	-145.7 nmol/L Standard Error 29.35	-174.5 nmol/L Standard Error 29.37	-124.9 nmol/L Standard Error 29.85	-201.6 nmol/L Standard Error 29.61	-250.0 nmol/L Standard Error 29.83	-209.6 nmol/L Standard Error 29.83	-223.6 nmol/L Standard Error 29.22	-283.9 nmol/L Standard Error 29.21	24.0 nmol/L Standard Error 29.13	2.5 nmol/L Standard Error 29.71	-36.6 nmol/L Standard Error 29.36	-96.3 nmol/L Standard Error 29.84

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	0.43 nm Standard Error 0.034	0.58 nm Standard Error 0.034	0.61 nm Standard Error 0.034	—
Change From Baseline in Mean LDL Particle Size Over Time (Grouped Analysis) Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	0.41 nm Standard Error 0.036	0.47 nm Standard Error 0.035	0.54 nm Standard Error 0.036	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Mean LDL Particle Size	0.43 nm Standard Error 0.059	0.49 nm Standard Error 0.058	0.44 nm Standard Error 0.060	0.61 nm Standard Error 0.059	0.61 nm Standard Error 0.060	0.58 nm Standard Error 0.060	0.68 nm Standard Error 0.058	0.73 nm Standard Error 0.058	-0.05 nm Standard Error 0.057	0.13 nm Standard Error 0.059	0.06 nm Standard Error 0.059	0.25 nm Standard Error 0.059

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean LDL particle size was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean LDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Mean LDL Particle Size	0.38 nm Standard Error 0.061	0.41 nm Standard Error 0.061	0.38 nm Standard Error 0.062	0.48 nm Standard Error 0.062	0.57 nm Standard Error 0.062	0.59 nm Standard Error 0.062	0.55 nm Standard Error 0.061	0.63 nm Standard Error 0.061	-0.06 nm Standard Error 0.061	-0.01 nm Standard Error 0.062	0.07 nm Standard Error 0.061	0.26 nm Standard Error 0.062

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26.

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Total Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	0.86 μMOL/L Standard Error 0.220	0.58 μMOL/L Standard Error 0.216	0.43 μMOL/L Standard Error 0.216	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Total Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	0.62 μMOL/L Standard Error 0.235	1.18 μMOL/L Standard Error 0.231	0.78 μMOL/L Standard Error 0.232	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Large Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	0.89 μMOL/L Standard Error 0.111	0.78 μMOL/L Standard Error 0.109	0.89 μMOL/L Standard Error 0.109	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Large Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	0.81 μMOL/L Standard Error 0.123	0.90 μMOL/L Standard Error 0.121	1.01 μMOL/L Standard Error 0.122	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Medium Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	1.38 μMOL/L Standard Error 0.195	1.16 μMOL/L Standard Error 0.191	1.63 μMOL/L Standard Error 0.191	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Medium Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	1.34 μMOL/L Standard Error 0.195	1.10 μMOL/L Standard Error 0.192	1.46 μMOL/L Standard Error 0.192	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Small Particles - Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	-1.35 μMOL/L Standard Error 0.261	-1.39 μMOL/L Standard Error 0.256	-2.12 μMOL/L Standard Error 0.256	—
Change From Baseline in High Density Lipoprotein (HDL) Particles Over Time (Grouped Analysis) Small Particles - Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	-1.45 μMOL/L Standard Error 0.261	-0.85 μMOL/L Standard Error 0.257	-1.73 μMOL/L Standard Error 0.258	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in HDL Particles Medium Particles	1.15 μmol/L Standard Error 0.332	0.65 μmol/L Standard Error 0.328	1.21 μmol/L Standard Error 0.338	0.97 μmol/L Standard Error 0.334	1.89 μmol/L Standard Error 0.338	2.06 μmol/L Standard Error 0.339	1.30 μmol/L Standard Error 0.326	2.31 μmol/L Standard Error 0.329	0.17 μmol/L Standard Error 0.325	-0.24 μmol/L Standard Error 0.333	-0.01 μmol/L Standard Error 0.332	0.81 μmol/L Standard Error 0.334
Change From Baseline to Week 12 in HDL Particles Small Particles	-1.09 μmol/L Standard Error 0.445	-0.63 μmol/L Standard Error 0.439	-0.92 μmol/L Standard Error 0.453	-1.18 μmol/L Standard Error 0.447	-2.82 μmol/L Standard Error 0.452	-2.82 μmol/L Standard Error 0.455	-1.84 μmol/L Standard Error 0.437	-2.84 μmol/L Standard Error 0.441	-0.07 μmol/L Standard Error 0.435	0.43 μmol/L Standard Error 0.447	0.27 μmol/L Standard Error 0.445	-0.25 μmol/L Standard Error 0.446
Change From Baseline to Week 12 in HDL Particles Total Particles	0.37 μmol/L Standard Error 0.375	0.55 μmol/L Standard Error 0.370	1.29 μmol/L Standard Error 0.382	0.75 μmol/L Standard Error 0.377	0.15 μmol/L Standard Error 0.382	0.40 μmol/L Standard Error 0.384	0.63 μmol/L Standard Error 0.369	0.60 μmol/L Standard Error 0.372	-0.08 μmol/L Standard Error 0.368	-0.06 μmol/L Standard Error 0.377	0.16 μmol/L Standard Error 0.375	0.90 μmol/L Standard Error 0.377
Change From Baseline to Week 12 in HDL Particles Large Particles	0.24 μmol/L Standard Error 0.189	0.50 μmol/L Standard Error 0.186	1.09 μmol/L Standard Error 0.192	0.95 μmol/L Standard Error 0.190	1.12 μmol/L Standard Error 0.192	1.06 μmol/L Standard Error 0.193	1.17 μmol/L Standard Error 0.186	1.06 μmol/L Standard Error 0.187	-0.21 μmol/L Standard Error 0.185	-0.29 μmol/L Standard Error 0.190	-0.10 μmol/L Standard Error 0.189	0.53 μmol/L Standard Error 0.190

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in levels of total, large, medium and small HDL particles was assessed by NMR lipid fractionation.

Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline NMR HDL particles as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in HDL Particles Total Particles	0.77 μmol/L Standard Error 0.400	1.31 μmol/L Standard Error 0.400	0.67 μmol/L Standard Error 0.407	1.15 μmol/L Standard Error 0.403	0.26 μmol/L Standard Error 0.406	0.83 μmol/L Standard Error 0.407	1.61 μmol/L Standard Error 0.398	0.77 μmol/L Standard Error 0.398	0.18 μmol/L Standard Error 0.397	0.43 μmol/L Standard Error 0.405	1.03 μmol/L Standard Error 0.400	0.37 μmol/L Standard Error 0.407
Change From Baseline to Week 26 in HDL Particles Large Particles	0.55 μmol/L Standard Error 0.210	0.75 μmol/L Standard Error 0.210	0.64 μmol/L Standard Error 0.213	1.13 μmol/L Standard Error 0.212	1.34 μmol/L Standard Error 0.213	1.26 μmol/L Standard Error 0.213	1.02 μmol/L Standard Error 0.209	0.95 μmol/L Standard Error 0.209	0.02 μmol/L Standard Error 0.208	-0.16 μmol/L Standard Error 0.212	0.39 μmol/L Standard Error 0.210	0.53 μmol/L Standard Error 0.213
Change From Baseline to Week 26 in HDL Particles Medium Particles	0.86 μmol/L Standard Error 0.332	0.67 μmol/L Standard Error 0.332	1.48 μmol/L Standard Error 0.338	1.47 μmol/L Standard Error 0.335	1.69 μmol/L Standard Error 0.337	1.71 μmol/L Standard Error 0.337	0.96 μmol/L Standard Error 0.331	2.01 μmol/L Standard Error 0.330	0.13 μmol/L Standard Error 0.330	0.16 μmol/L Standard Error 0.336	0.54 μmol/L Standard Error 0.332	0.81 μmol/L Standard Error 0.338
Change From Baseline to Week 26 in HDL Particles Small Particles	-0.68 μmol/L Standard Error 0.444	-0.17 μmol/L Standard Error 0.444	-1.35 μmol/L Standard Error 0.452	-1.47 μmol/L Standard Error 0.448	-2.77 μmol/L Standard Error 0.452	-2.21 μmol/L Standard Error 0.452	-0.40 μmol/L Standard Error 0.443	-2.24 μmol/L Standard Error 0.442	0.00 μmol/L Standard Error 0.441	0.41 μmol/L Standard Error 0.450	0.10 μmol/L Standard Error 0.444	-0.78 μmol/L Standard Error 0.452

SECONDARY outcome

Timeframe: Baseline and Weeks 12 and 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation at Weeks 12 and 26.

This analysis compared the groupings of participants who received the combination of pioglitazone with each dose of alogliptin with the grouping of participants who received pioglitazone alone. Least squares means are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=387 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=390 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=390 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) Week 12 (n=332, 345, 343)	—	—	—	—	—	—	—	—	0.11 nm Standard Error 0.013	0.13 nm Standard Error 0.013	0.16 nm Standard Error 0.013	—
Change From Baseline in Mean HDL Particle Size Over Time (Grouped Analysis) Week 26 (n=348, 359, 357)	—	—	—	—	—	—	—	—	0.11 nm Standard Error 0.015	0.12 nm Standard Error 0.014	0.17 nm Standard Error 0.014	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=114 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=117 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=110 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=113 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=110 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=109 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=119 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=113 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=114 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=113 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 12 in Mean HDL Particle Size	0.07 nm Standard Error 0.023	0.09 nm Standard Error 0.023	0.10 nm Standard Error 0.023	0.15 nm Standard Error 0.023	0.17 nm Standard Error 0.023	0.18 nm Standard Error 0.024	0.17 nm Standard Error 0.023	0.21 nm Standard Error 0.023	0.00 nm Standard Error 0.023	0.00 nm Standard Error 0.023	0.00 nm Standard Error 0.023	0.06 nm Standard Error 0.023

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Full analysis set where Baseline and at least 1 postbaseline assessment were available. Last observation carried forward imputation was utilized.

The change from Baseline in mean HDL particle size was assessed by NMR lipid fractionation. Least squares means are from are from an ANCOVA model with treatment and geographic region as class variables, and baseline metformin dose and baseline mean HDL particle size as continuous covariates.

Outcome measures

Measure	Alogliptin 12.5 + Pioglitazone 15 n=120 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=120 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=118 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=116 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=121 Participants Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=121 Participants Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Pioglitazone Alone n=122 Participants Alogliptin placebo plus all active pioglitazone groups (15, 30, and 45 mg).	Alogliptin 12.5 + Pioglitazone n=117 Participants Alogliptin 12.5 mg plus all active pioglitazone (15, 30, and 45 mg).	Alogliptin 25 + Pioglitazone n=120 Participants Alogliptin 25 mg plus all active pioglitazone (15, 30, and 45 mg).	Placebo + Pioglitazone 15 n=116 Participants Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.
Change From Baseline to Week 26 in Mean HDL Particle Size	0.06 nm Standard Error 0.025	0.11 nm Standard Error 0.025	0.10 nm Standard Error 0.025	0.15 nm Standard Error 0.025	0.20 nm Standard Error 0.025	0.19 nm Standard Error 0.025	0.16 nm Standard Error 0.025	0.19 nm Standard Error 0.025	0.03 nm Standard Error 0.025	0.00 nm Standard Error 0.025	0.07 nm Standard Error 0.025	0.06 nm Standard Error 0.025

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Alogliptin 12.5 + Placebo

Serious events: 5 serious events

Other events: 40 other events

Deaths: 0 deaths

Alogliptin 25 + Placebo

Serious events: 6 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo + Pioglitazone 15

Serious events: 1 serious events

Other events: 51 other events

Deaths: 0 deaths

Alogliptin 12.5 + Pioglitazone 15

Serious events: 2 serious events

Other events: 45 other events

Deaths: 0 deaths

Alogliptin 25 + Pioglitazone 15

Serious events: 1 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo + Pioglitazone 30

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Alogliptin 12.5 + Pioglitazone 30

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Alogliptin 25 + Pioglitazone 30

Serious events: 6 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo + Pioglitazone 45

Serious events: 10 serious events

Other events: 40 other events

Deaths: 0 deaths

Alogliptin 12.5 + Pioglitazone 45

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

Alogliptin 25 + Pioglitazone 45

Serious events: 5 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Placebo n=128 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Placebo n=129 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 15 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 15 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
General disorders Non-cardiac chest pain	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Cardiac disorders Angina unstable	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Cardiac disorders Coronary artery disease	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Cardiac disorders Coronary artery stenosis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Cardiac disorders Myocardial infarction	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Cardiac disorders Myocardial ischaemia	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Gastritis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Pancreatitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Periodontitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Reflux oesophagitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Umbilical hernia	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
General disorders Pyrexia	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
General disorders Sudden cardiac death	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Hepatobiliary disorders Cholangitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Hepatobiliary disorders Cholecystitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Hepatobiliary disorders Hepatitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Appendicitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Pneumonia	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Arthritis bacterial	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Bronchopneumonia	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Gastroenteritis viral	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Lower respiratory tract infection	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Osteomyelitis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Perirectal abscess	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Pyelonephritis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Pyelonephritis acute	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Urinary tract infection	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Injury, poisoning and procedural complications Foreign body in eye	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Carotid artery occlusion	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Cerebrovascular accident	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Convulsion	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Disturbance in attention	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Ischaemic stroke	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Lacunar infarction	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Migraine with aura	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Nerve compression	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Syncope	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Psychiatric disorders Anxiety	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Renal and urinary disorders Calculus ureteric	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Renal and urinary disorders Nephrolithiasis	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Respiratory, thoracic and mediastinal disorders Lung cyst benign	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Vascular disorders Peripheral vascular disorder	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.

Other adverse events

Measure	Placebo n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Placebo n=128 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Placebo n=129 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 15 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 15 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 15 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 15 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 30 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 30 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 30 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.	Placebo + Pioglitazone 45 n=129 participants at risk Alogliptin placebo-matching tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 12.5 + Pioglitazone 45 n=130 participants at risk Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.	Alogliptin 25 + Pioglitazone 45 n=130 participants at risk Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 45 mg, tablets, orally, once daily for up to 26 weeks.
Infections and infestations Nasopharyngitis	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.9% 9/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Headache	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	7.0% 9/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	12.4% 16/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Urinary tract infection	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Musculoskeletal and connective tissue disorders Back pain	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	9.2% 12/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Diarrhoea	8.5% 11/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Influenza	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	7.0% 9/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Nervous system disorders Dizziness	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Vascular disorders Hypertension	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.9% 9/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Infections and infestations Upper respiratory tract infection	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	6.2% 8/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Metabolism and nutrition disorders Hypertriglyceridaemia	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.5% 7/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.9% 5/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
General disorders Oedema peripheral	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.7% 6/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	4.6% 6/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Blood and lymphatic system disorders Anaemia	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.1% 4/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.
Gastrointestinal disorders Abdominal pain upper	1.6% 2/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/128 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	5.4% 7/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	1.5% 2/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.77% 1/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	2.3% 3/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.78% 1/129 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	3.8% 5/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.	0.00% 0/130 • Adverse events were collected from the time of informed consent until the end of the study, and from spontaneous reporting for 30 days after the end of treatment. At each study visit, the investigator assessed whether any events had occurred. Patients could report events at any other time during the study. All events, whether reported by the patient or observed by the investigator, were documented, whether or not the investigator concluded the event to be related to the drug treatment.

Additional Information

Sr. VP, Clinical Science

Takeda Global Research and Development Center, Inc.

Phone: 800-778-2860

Email: clinicaltrialregistry@tpna.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER