Trial Outcomes & Findings for The CANTATA-M (CANagliflozin Treatment and Trial Analysis - Monotherapy) Trial (NCT NCT01081834)

NCT ID: NCT01081834

Last Updated: 2017-02-23

Results Overview

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 678 participants
• Primary outcome timeframe: Day 1 (Baseline) and Week 26
• Results posted on: 2017-02-23

Participant Flow

This study evaluated the efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. The study was conducted between 08 February 2010 and 18 August 2011 and recruited patients from 90 study centers in 17 countries worldwide.

678 patients were enrolled into the study; 587 patients in the main study and 91 patients in the high glycemic substudy. 584 patients in the main study and all 91 patients in the high glycemic substudy received at least one dose of study drug and were included in the modified intent-to-treat (mITT) analyses sets and the safety analyses sets.

Participant milestones

Measure	Main Study: Placebo/Sitagliptin In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Main Study: Canagliflozin 100 mg In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Main Study: Canagliflozin 300 mg In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks.	High Glycemic Substudy: Canagliflozin 100 mg In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52.	High Glycemic Substudy: Canagliflozin 300 mg In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52.
Core Period: Baseline to Week 26 COMPLETED	160	172	175	40	40
Core Period: Baseline to Week 26 STARTED	192	195	197	47	44
Core Period: Baseline to Week 26 NOT COMPLETED	32	23	22	7	4
Extension Period: Week 26 to Week 52 STARTED	155	170	170	0	0
Extension Period: Week 26 to Week 52 COMPLETED	135	152	165	0	0
Extension Period: Week 26 to Week 52 NOT COMPLETED	20	18	5	0	0

Reasons for withdrawal

Measure	Main Study: Placebo/Sitagliptin In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Main Study: Canagliflozin 100 mg In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Main Study: Canagliflozin 300 mg In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks.	High Glycemic Substudy: Canagliflozin 100 mg In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52.	High Glycemic Substudy: Canagliflozin 300 mg In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks only. No patients received treatment during the period Week 26 to Week 52.
Core Period: Baseline to Week 26 Pregnancy	1	0	0	0	0
Core Period: Baseline to Week 26 Adverse Event	2	5	3	1	1
Core Period: Baseline to Week 26 Death	1	0	0	0	0
Core Period: Baseline to Week 26 Lost to Follow-up	2	2	5	0	0
Core Period: Baseline to Week 26 Protocol Violation	0	4	0	0	2
Core Period: Baseline to Week 26 Withdrawal by Subject	15	3	9	3	1
Core Period: Baseline to Week 26 Noncompliance with study drug	3	4	2	2	0
Core Period: Baseline to Week 26 Unable to take rescue therapy	1	0	0	0	0
Core Period: Baseline to Week 26 Other	4	4	3	1	0
Core Period: Baseline to Week 26 Lack of efficacy on rescue therapy	3	1	0	0	0
Extension Period: Week 26 to Week 52 Adverse Event	1	0	0	0	0
Extension Period: Week 26 to Week 52 Death	1	0	0	0	0
Extension Period: Week 26 to Week 52 Lost to Follow-up	4	4	0	0	0
Extension Period: Week 26 to Week 52 Protocol Violation	0	1	0	0	0
Extension Period: Week 26 to Week 52 Withdrawal by Subject	1	2	0	0	0
Extension Period: Week 26 to Week 52 Unable to take rescue therapy	1	0	1	0	0
Extension Period: Week 26 to Week 52 Creatinine or eGFR withdrawal criteria	1	4	0	0	0
Extension Period: Week 26 to Week 52 Other	4	5	4	0	0
Extension Period: Week 26 to Week 52 Lack of efficacy on rescue therapy	7	1	0	0	0
Extension Period: Week 26 to Week 52 Physician Decision	0	1	0	0	0

Baseline Characteristics

The CANTATA-M (CANagliflozin Treatment and Trial Analysis - Monotherapy) Trial

Baseline characteristics by cohort

Measure	Main Study: Placebo/Sitagliptin n=192 Participants In the Main Study, each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Main Study: Canagliflozin 100 mg n=195 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Main Study: Canagliflozin 300 mg n=197 Participants In the Main Study, each patient received 300 mg of canagliflozin once daily for 52 weeks.	High Glycemic Substudy: Canagliflozin 100 mg n=47 Participants In the High Glycemic Substudy, each patient received 100 mg of canagliflozin once daily for 26 weeks.	High Glycemic Substudy: Canagliflozin 300 mg n=44 Participants In the High Glycemic Substudy, each patient received 300 mg of canagliflozin once daily for 26 weeks.	Total n=675 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	150 Participants n=5 Participants	156 Participants n=7 Participants	160 Participants n=5 Participants	42 Participants n=4 Participants	41 Participants n=21 Participants	549 Participants n=10 Participants
Age, Categorical >=65 years	42 Participants n=5 Participants	39 Participants n=7 Participants	37 Participants n=5 Participants	5 Participants n=4 Participants	3 Participants n=21 Participants	126 Participants n=10 Participants
Age, Continuous	55.7 years STANDARD_DEVIATION 10.88 • n=5 Participants	55.1 years STANDARD_DEVIATION 10.83 • n=7 Participants	55.3 years STANDARD_DEVIATION 10.17 • n=5 Participants	49.7 years STANDARD_DEVIATION 11.12 • n=4 Participants	48.8 years STANDARD_DEVIATION 10.92 • n=21 Participants	54.5 years STANDARD_DEVIATION 10.85 • n=10 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	114 Participants n=7 Participants	108 Participants n=5 Participants	24 Participants n=4 Participants	25 Participants n=21 Participants	375 Participants n=10 Participants
Sex: Female, Male Male	88 Participants n=5 Participants	81 Participants n=7 Participants	89 Participants n=5 Participants	23 Participants n=4 Participants	19 Participants n=21 Participants	300 Participants n=10 Participants
Region of Enrollment AUSTRIA	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	4 participants n=10 Participants
Region of Enrollment COLOMBIA	8 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	3 participants n=4 Participants	0 participants n=21 Participants	25 participants n=10 Participants
Region of Enrollment ESTONIA	6 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	16 participants n=10 Participants
Region of Enrollment GUATEMALA	10 participants n=5 Participants	10 participants n=7 Participants	13 participants n=5 Participants	9 participants n=4 Participants	10 participants n=21 Participants	52 participants n=10 Participants
Region of Enrollment ICELAND	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants	20 participants n=10 Participants
Region of Enrollment INDIA	8 participants n=5 Participants	11 participants n=7 Participants	8 participants n=5 Participants	5 participants n=4 Participants	2 participants n=21 Participants	34 participants n=10 Participants
Region of Enrollment LITHUANIA	17 participants n=5 Participants	10 participants n=7 Participants	12 participants n=5 Participants	2 participants n=4 Participants	1 participants n=21 Participants	42 participants n=10 Participants
Region of Enrollment MALAYSIA	6 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants	1 participants n=4 Participants	0 participants n=21 Participants	16 participants n=10 Participants
Region of Enrollment MEXICO	19 participants n=5 Participants	23 participants n=7 Participants	19 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants	65 participants n=10 Participants
Region of Enrollment PHILIPPINES	3 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	4 participants n=4 Participants	4 participants n=21 Participants	21 participants n=10 Participants
Region of Enrollment POLAND	1 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	8 participants n=10 Participants
Region of Enrollment ROMANIA	20 participants n=5 Participants	16 participants n=7 Participants	18 participants n=5 Participants	2 participants n=4 Participants	4 participants n=21 Participants	60 participants n=10 Participants
Region of Enrollment SOUTH AFRICA	9 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	1 participants n=4 Participants	2 participants n=21 Participants	29 participants n=10 Participants
Region of Enrollment SOUTH KOREA	10 participants n=5 Participants	8 participants n=7 Participants	7 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants	27 participants n=10 Participants
Region of Enrollment SPAIN	3 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	8 participants n=10 Participants
Region of Enrollment SWEDEN	11 participants n=5 Participants	18 participants n=7 Participants	18 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants	48 participants n=10 Participants
Region of Enrollment UNITED STATES	56 participants n=5 Participants	62 participants n=7 Participants	52 participants n=5 Participants	15 participants n=4 Participants	15 participants n=21 Participants	200 participants n=10 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Outcome measures

Measure	Placebo n=189 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=191 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=194 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in HbA1c From Baseline to Week 26 (Main Study)	0.14 Percent Standard Error 0.065	-0.77 Percent Standard Error 0.065	-1.03 Percent Standard Error 0.064

PRIMARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in HbA1c from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=46 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in HbA1c From Baseline to Week 26 (High Glycemic Substudy)	—	-2.13 Percent Standard Error 0.220	-2.56 Percent Standard Error 0.227

SECONDARY outcome

Timeframe: Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the percentage of patients with HbA1c <7% at Week 26. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the percentage.

Outcome measures

Measure	Placebo n=189 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=191 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=194 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percentage of Patients With HbA1c <7% at Week 26 (Main Study)	20.6 Percentage of patients	44.5 Percentage of patients	62.4 Percentage of patients

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Outcome measures

Measure	Placebo n=184 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=188 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=192 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (Main Study)	8.33 mg/dL Standard Error 2.448	-27.2 mg/dL Standard Error 2.412	-35.0 mg/dL Standard Error 2.391

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Outcome measures

Measure	Placebo n=126 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=154 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=157 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (Main Study)	5.19 mg/dL Standard Error 4.204	-42.9 mg/dL Standard Error 3.763	-58.8 mg/dL Standard Error 3.741

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

Outcome measures

Measure	Placebo n=190 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=192 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=194 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in Body Weight From Baseline to Week 26 (Main Study)	-0.6 Percent change Standard Error 0.2	-2.8 Percent change Standard Error 0.2	-3.9 Percent change Standard Error 0.2

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean change.

Outcome measures

Measure	Placebo n=190 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=192 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=195 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (Main Study)	0.38 mmHg Standard Error 0.780	-3.34 mmHg Standard Error 0.775	-5.04 mmHg Standard Error 0.769

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean percent change in triglycerides from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

Outcome measures

Measure	Placebo n=171 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=183 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=183 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in Triglycerides From Baseline to Week 26 (Main Study)	7.8 Percent change Standard Error 3.5	2.5 Percent change Standard Error 3.3	-2.4 Percent change Standard Error 3.3

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean percent change in HDL-C from Baseline to Week 26 for each treatment group. The statistical analyses show the treatment differences (ie, each canagliflozin group minus placebo) in the LS mean percent change.

Outcome measures

Measure	Placebo n=170 Participants In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=182 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=183 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (Main Study)	4.4 Percent change Standard Error 1.4	11.2 Percent change Standard Error 1.4	10.5 Percent change Standard Error 1.4

SECONDARY outcome

Timeframe: Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the percentage of patients with HbA1c <7% at Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=46 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percentage of Patients With HbA1c <7% at Week 26 (High Glycemic Substudy)	—	17.4 Percentage of patients	11.6 Percentage of patients

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in FPG from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=45 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 (High Glycemic Substudy)	—	-81.7 mg/dL Standard Error 6.459	-86.3 mg/dL Standard Error 6.553

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in 2-hour post-prandial glucose from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=30 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=34 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in 2-hour Post-prandial Glucose From Baseline to Week 26 (High Glycemic Substudy)	—	-118 mg/dL Standard Error 10.179	-126 mg/dL Standard Error 9.437

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean percent change in body weight from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=46 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in Body Weight From Baseline to Week 26 (High Glycemic Substudy)	—	-3.0 Percent change Standard Error 0.6	-3.8 Percent change Standard Error 0.6

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares (LS) mean change in SBP from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=46 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 (High Glycemic Substudy)	—	-4.47 mmHg Standard Error 1.754	-4.97 mmHg Standard Error 1.800

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values.

The table below shows the least-squares mean percent change in triglycerides from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=44 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in Triglycerides From Baseline to Week 26 (High Glycemic Substudy)	—	-0.6 Percent change Standard Error 7.4	-12.7 Percent change Standard Error 7.5

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Week 26

Population: Analysis used mITT analysis set (all randomized patients who received at least 1 dose of study drug). Last-observation-carried-forward method used for missing Week 26 values. Measurements taken pre-rescue used as last observation in patients receiving glycemic rescue therapy. Table includes only patients with both baseline and post baseline values

The table below shows the least-squares mean percent change in HDL-C from Baseline to Week 26 for each treatment group in patients randomized to the High Glycemic Substudy.

Outcome measures

Measure	Placebo In the Main Study, each patient recieved matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52.	Canagliflozin 100 mg n=44 Participants In the Main Study, each patient received 100 mg of canagliflozin once daily for 52 weeks.	Canagliflozin 300 mg n=43 Participants In the Main Study, each pateint received 300 mg of canagliflozin once daily for 52 weeks.
Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 (High Glycemic Substudy)	—	2.4 Percent change Standard Error 2.9	10.8 Percent change Standard Error 2.9

Adverse Events

Main Study (Baseline to Week 26): Placebo

Serious events: 4 serious events

Other events: 38 other events

Deaths: 0 deaths

Main Study (Baseline to Week 26): Cana 100 mg

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

Main Study (Baseline to Week 26): Cana 300 mg

Serious events: 2 serious events

Other events: 51 other events

Deaths: 0 deaths

Main Study (Baseline to Week 52): Placebo/Sitagliptin

Serious events: 11 serious events

Other events: 63 other events

Deaths: 0 deaths

Main Study (Baseline to Week 52): Cana 100 mg

Serious events: 11 serious events

Other events: 54 other events

Deaths: 0 deaths

Main Study (Baseline to Week 52): Cana 300 mg

Serious events: 5 serious events

Other events: 69 other events

Deaths: 0 deaths

High Glycemic Substudy (Baseline to Week 26): Cana 100 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

High Glycemic Substudy (Baseline to Week 26): Cana 300 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Main Study (Baseline to Week 26): Placebo n=192 participants at risk Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 26): Cana 100 mg n=195 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 26): Cana 300 mg n=197 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 52): Placebo/Sitagliptin n=192 participants at risk Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 52.	Main Study (Baseline to Week 52): Cana 100 mg n=195 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52.	Main Study (Baseline to Week 52): Cana 300 mg n=197 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52.	High Glycemic Substudy (Baseline to Week 26): Cana 100 mg n=47 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26.	High Glycemic Substudy (Baseline to Week 26): Cana 300 mg n=44 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26.
Infections and infestations Cellulitis	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Diverticulitis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Coronary artery disease	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Abdominal pain	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Intestinal obstruction	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Nausea	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Vomiting	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Ischaemic hepatitis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Abscess limb	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Bacterial prostatitis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pneumonia	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Septic shock	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Ankle fracture	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Brain herniation	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Wound	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Haemorrhage intracranial	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Renal and urinary disorders Renal colic	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Renal and urinary disorders Renal failure acute	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	1.0% 2/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	1.0% 2/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Vascular disorders Deep vein thrombosis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Vascular disorders Thrombosis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Myocardial infarction	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Cardiac disorders Pericardial effusion	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Abdominal hernia	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Inguinal hernia	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Umbilical hernia	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Liver disorder	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Appendicitis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Gastrointestinal infection	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pulmonary tuberculosis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Viral pericarditis	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Skeletal injury	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Injury, poisoning and procedural complications Spinal column injury	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.52% 1/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.51% 1/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Investigations Hepatic enzyme increased	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	2.3% 1/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

Other adverse events

Measure	Main Study (Baseline to Week 26): Placebo n=192 participants at risk Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 26): Cana 100 mg n=195 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 26): Cana 300 mg n=197 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 26.	Main Study (Baseline to Week 52): Placebo/Sitagliptin n=192 participants at risk Each patient received matching placebo once daily for 26 weeks and were then switched from placebo to 100 mg of sitagliptin once daily until Week 52. Data are presented for Baseline to Week 52.	Main Study (Baseline to Week 52): Cana 100 mg n=195 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52.	Main Study (Baseline to Week 52): Cana 300 mg n=197 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 52 weeks. Data are presented for Baseline to Week 52.	High Glycemic Substudy (Baseline to Week 26): Cana 100 mg n=47 participants at risk Each patient received 100 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26.	High Glycemic Substudy (Baseline to Week 26): Cana 300 mg n=44 participants at risk Each patient received 300 mg of canagliflozin (Cana) once daily for 26 weeks. Data are only available for Baseline to Week 26.
Infections and infestations Nasopharyngitis	5.2% 10/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.1% 10/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.1% 16/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.8% 15/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.2% 14/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.2% 20/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.3% 2/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.8% 3/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Upper respiratory tract infection	5.7% 11/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	3.6% 7/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.6% 9/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.4% 18/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.1% 8/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.1% 14/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Urinary tract infection	4.2% 8/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.2% 14/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.6% 9/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.7% 11/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.2% 16/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.1% 12/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.4% 3/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.5% 2/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Back pain	3.1% 6/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	2.6% 5/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.1% 12/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.7% 9/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	2.6% 5/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.6% 15/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Headache	3.6% 7/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.2% 14/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.1% 12/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.2% 12/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.7% 19/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.6% 17/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	2.1% 1/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.8% 3/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Influenza	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	3.6% 7/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.2% 12/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.1% 8/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.8% 13/192 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.1% 10/195 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	1.5% 3/197 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/47 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/44 • Adverse events were reported for the duration of the study; each patient participated in the study for approximately 52 weeks. The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

Additional Information

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Janssen Research & Development, LLC

Phone: 1-800-526-7736

Results disclosure agreements

• Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
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