Trial Outcomes & Findings for Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes (NCT NCT01549964)

Last Updated: 2016-06-02

Results Overview

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

916 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2016-06-02

Participant Flow

Participants took part in the study at 168 investigative sites in Australia, Bulgaria, Croatia, Czech Republic, Hungary, Italy, Korea, Republic, Malaysia, Slovakia, Thailand and the United States from 05 April 2012 to 27 March 2014.

Participants with a diagnosis of Type 2 Diabetes Mellitus were randomly enrolled in 1 of 4 treatment groups in a 1:2:2:2 ratio, once a day placebo, 100 mg sitagliptin, 25 mg fasiglifam or 50 mg fasiglifam in combination with metformin.

Participant milestones

Participant milestones
Measure	Placebo Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
24-Week Treatment Period STARTED	132	260	263	261
24-Week Treatment Period Safety Analysis Set=Received Treatment	132	260	263	260
24-Week Treatment Period COMPLETED	71	149	147	140
24-Week Treatment Period NOT COMPLETED	61	111	116	121
80-Week Extension Period STARTED	66	138	140	137
80-Week Extension Period COMPLETED	0	0	0	0
80-Week Extension Period NOT COMPLETED	66	138	140	137

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
24-Week Treatment Period Study Terminated by Sponsor	50	104	104	105
24-Week Treatment Period Voluntary Withdrawal	6	3	3	8
24-Week Treatment Period Pretreatment Event/Adverse Event	1	4	4	4
24-Week Treatment Period Lost to Follow-up	1	0	1	2
24-Week Treatment Period Lack of Efficacy	1	0	1	1
24-Week Treatment Period Other	1	0	1	0
24-Week Treatment Period Metformin/Sitagliptin Contraindication	0	0	1	0
24-Week Treatment Period Randomized but Not Treated	0	0	0	1
24-Week Treatment Period Completion Status Unknown	1	0	1	0
80-Week Extension Period Pregnancy	0	0	1	0
80-Week Extension Period Study Terminated by Sponsor	65	137	132	132
80-Week Extension Period Voluntary Withdrawal	0	1	4	2
80-Week Extension Period Lost to Follow-up	1	0	2	1
80-Week Extension Period Pretreatment Event/Adverse Event	0	0	1	2

Baseline Characteristics

Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=132 Participants Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg n=260 Participants Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg n=263 Participants Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg n=261 Participants Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Total n=916 Participants Total of all reporting groups
Age, Continuous	55.6 years STANDARD_DEVIATION 9.72 • n=5 Participants	55.8 years STANDARD_DEVIATION 9.84 • n=7 Participants	56.3 years STANDARD_DEVIATION 9.58 • n=5 Participants	56.0 years STANDARD_DEVIATION 9.37 • n=4 Participants	56.0 years STANDARD_DEVIATION 9.60 • n=21 Participants
Age, Customized < 65 years	107 participants n=5 Participants	214 participants n=7 Participants	216 participants n=5 Participants	220 participants n=4 Participants	757 participants n=21 Participants
Age, Customized ≥ 65 years	25 participants n=5 Participants	46 participants n=7 Participants	47 participants n=5 Participants	41 participants n=4 Participants	159 participants n=21 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	103 Participants n=7 Participants	127 Participants n=5 Participants	126 Participants n=4 Participants	422 Participants n=21 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	157 Participants n=7 Participants	136 Participants n=5 Participants	135 Participants n=4 Participants	494 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	5 participants n=21 Participants
Race/Ethnicity, Customized Asian	12 participants n=5 Participants	30 participants n=7 Participants	28 participants n=5 Participants	26 participants n=4 Participants	96 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	13 participants n=7 Participants	19 participants n=5 Participants	12 participants n=4 Participants	52 participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized White	112 participants n=5 Participants	216 participants n=7 Participants	214 participants n=5 Participants	217 participants n=4 Participants	759 participants n=21 Participants
Race/Ethnicity, Customized Multiracial	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Data Not Available	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 participants n=5 Participants	29 participants n=7 Participants	28 participants n=5 Participants	28 participants n=4 Participants	98 participants n=21 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	28 participants n=5 Participants	59 participants n=7 Participants	53 participants n=5 Participants	55 participants n=4 Participants	195 participants n=21 Participants
Race/Ethnicity, Customized Not Collected	91 participants n=5 Participants	172 participants n=7 Participants	182 participants n=5 Participants	178 participants n=4 Participants	623 participants n=21 Participants
Region of Enrollment Australia	3 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	5 participants n=4 Participants	18 participants n=21 Participants
Region of Enrollment Bulgaria	3 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants	24 participants n=21 Participants
Region of Enrollment Croatia	4 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	6 participants n=4 Participants	24 participants n=21 Participants
Region of Enrollment Czech Republic	8 participants n=5 Participants	15 participants n=7 Participants	14 participants n=5 Participants	14 participants n=4 Participants	51 participants n=21 Participants
Region of Enrollment Hungary	29 participants n=5 Participants	56 participants n=7 Participants	61 participants n=5 Participants	60 participants n=4 Participants	206 participants n=21 Participants
Region of Enrollment Italy	1 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	2 participants n=4 Participants	9 participants n=21 Participants
Region of Enrollment Korea, Republic Of	2 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	12 participants n=21 Participants
Region of Enrollment Malaysia	2 participants n=5 Participants	8 participants n=7 Participants	7 participants n=5 Participants	8 participants n=4 Participants	25 participants n=21 Participants
Region of Enrollment Slovakia	34 participants n=5 Participants	66 participants n=7 Participants	65 participants n=5 Participants	66 participants n=4 Participants	231 participants n=21 Participants
Region of Enrollment Thailand	7 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	14 participants n=4 Participants	48 participants n=21 Participants
Region of Enrollment United States	39 participants n=5 Participants	76 participants n=7 Participants	76 participants n=5 Participants	77 participants n=4 Participants	268 participants n=21 Participants
Weight	91.15 kg STANDARD_DEVIATION 18.988 • n=5 Participants	91.41 kg STANDARD_DEVIATION 19.664 • n=7 Participants	91.44 kg STANDARD_DEVIATION 17.859 • n=5 Participants	91.53 kg STANDARD_DEVIATION 18.772 • n=4 Participants	91.42 kg STANDARD_DEVIATION 18.776 • n=21 Participants
Height	168.2 cm STANDARD_DEVIATION 10.08 • n=5 Participants	169.4 cm STANDARD_DEVIATION 10.74 • n=7 Participants	168.5 cm STANDARD_DEVIATION 10.53 • n=5 Participants	168.4 cm STANDARD_DEVIATION 9.85 • n=4 Participants	168.7 cm STANDARD_DEVIATION 10.34 • n=21 Participants
Body Mass Index (BMI)	32.06 kg/m^2 STANDARD_DEVIATION 5.070 • n=5 Participants	31.68 kg/m^2 STANDARD_DEVIATION 5.282 • n=7 Participants	32.11 kg/m^2 STANDARD_DEVIATION 5.126 • n=5 Participants	32.16 kg/m^2 STANDARD_DEVIATION 5.651 • n=4 Participants	32.00 kg/m^2 STANDARD_DEVIATION 5.312 • n=21 Participants
BMI Category < 30 kg/m^2	53 participants n=5 Participants	106 participants n=7 Participants	92 participants n=5 Participants	101 participants n=4 Participants	352 participants n=21 Participants
BMI Category ≥ 30 kg/m^2	79 participants n=5 Participants	154 participants n=7 Participants	170 participants n=5 Participants	159 participants n=4 Participants	562 participants n=21 Participants
BMI Category Data Not Available	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants
Glycosylated Hemoglobin (HbA1c)	8.34 percent STANDARD_DEVIATION 0.739 • n=5 Participants	8.35 percent STANDARD_DEVIATION 0.694 • n=7 Participants	8.41 percent STANDARD_DEVIATION 0.712 • n=5 Participants	8.43 percent STANDARD_DEVIATION 0.765 • n=4 Participants	NA percent STANDARD_DEVIATION NA • n=21 Participants
HbA1c Category < 8.5%	80 participants n=5 Participants	156 participants n=7 Participants	154 participants n=5 Participants	148 participants n=4 Participants	538 participants n=21 Participants
HbA1c Category ≥ 8.5%	52 participants n=5 Participants	104 participants n=7 Participants	109 participants n=5 Participants	112 participants n=4 Participants	377 participants n=21 Participants
HbA1c Category Data Not Available	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Duration of Diabetes	6.655 years STANDARD_DEVIATION 6.262 • n=5 Participants	5.940 years STANDARD_DEVIATION 4.942 • n=7 Participants	6.726 years STANDARD_DEVIATION 4.615 • n=5 Participants	6.375 years STANDARD_DEVIATION 5.214 • n=4 Participants	6.393 years STANDARD_DEVIATION 5.143 • n=21 Participants
Fasting Plasma Glucose	178.4 ng/dL STANDARD_DEVIATION 36.94 • n=5 Participants	175.6 ng/dL STANDARD_DEVIATION 37.67 • n=7 Participants	179.0 ng/dL STANDARD_DEVIATION 33.52 • n=5 Participants	180.0 ng/dL STANDARD_DEVIATION 37.98 • n=4 Participants	NA ng/dL STANDARD_DEVIATION NA • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized. A participant was included in the analyses when there was both a Baseline and at least 1 Post-baseline value at Week 24.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg n=145 Participants Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg n=144 Participants Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg n=138 Participants Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	-0.19 Percent Standard Error 0.098	-1.07 Percent Standard Error 0.074	-0.75 Percent Standard Error 0.073	-1.01 Percent Standard Error 0.074

SECONDARY outcome

Timeframe: 24 Weeks

Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized

Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg n=145 Participants Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg n=144 Participants Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg n=138 Participants Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Incidence of HbA1c <7%	14.9 percentage of participants	42.8 percentage of participants	24.3 percentage of participants	37.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

The change between FPG collected at week 24 relative to Baseline. A MMRM model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=67 Participants Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg n=145 Participants Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg n=142 Participants Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg n=135 Participants Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Change From Baseline in Fasting Plasma Glucose (FPG)	-1.6 mg/dL Standard Error 4.07	-21.7 mg/dL Standard Error 3.13	-26.9 mg/dL Standard Error 3.13	-32.9 mg/dL Standard Error 3.18

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Sitagliptin 100 mg

Serious events: 10 serious events

Other events: 16 other events

Deaths: 0 deaths

Fasiglifam 25 mg

Serious events: 14 serious events

Other events: 18 other events

Deaths: 0 deaths

Fasiglifam 50 mg

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=132 participants at risk Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Sitagliptin 100 mg n=260 participants at risk Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 25 mg n=263 participants at risk Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Fasiglifam 50 mg n=260 participants at risk Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
Metabolism and nutrition disorders Hyperglycaemia	10.6% 14/132 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.5% 9/260 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.2% 11/263 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.7% 7/260 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	2.3% 3/132 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.1% 8/260 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.7% 7/263 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.4% 14/260 • First dose of study medication to 30 day past last dose of study medication (Up to 637 days) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER