Trial Outcomes & Findings for A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus (NCT NCT02390050)

Last Updated: 2021-06-29

Results Overview

Mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA) with baseline HbA1c as a covariate will be fit to the available data, incorporating all visits at which HbA1c was measured for each subject including scheduled visits at Weeks 2, 6, and 12 as well as unscheduled visits for measurements of HbA1c. Treatment (placebo, 5 mg, 10 mg, 20 mg), study center, prior anti-diabetic treatment status, study visit and treatment-by-visit interaction will be applied as fixed effects and subject as a random effect. The least square mean (LSM) change from baseline to Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

292 participants

Primary outcome timeframe

12 weeks

Results posted on

2021-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Overall Study STARTED	72	72	72	76
Overall Study COMPLETED	65	67	68	69
Overall Study NOT COMPLETED	7	5	4	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=72 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=76 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Total n=292 Participants Total of all reporting groups
Age, Continuous	58.8 years STANDARD_DEVIATION 10.42 • n=5 Participants	59.0 years STANDARD_DEVIATION 10.22 • n=7 Participants	59.4 years STANDARD_DEVIATION 8.99 • n=5 Participants	59.5 years STANDARD_DEVIATION 10.81 • n=4 Participants	59.2 years STANDARD_DEVIATION 10.99 • n=21 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	25 Participants n=7 Participants	31 Participants n=5 Participants	26 Participants n=4 Participants	112 Participants n=21 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	47 Participants n=7 Participants	41 Participants n=5 Participants	50 Participants n=4 Participants	180 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	17 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	58 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	57 Participants n=5 Participants	55 Participants n=7 Participants	58 Participants n=5 Participants	61 Participants n=4 Participants	231 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants	38 Participants n=7 Participants	39 Participants n=5 Participants	41 Participants n=4 Participants	155 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	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
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	30 Participants n=21 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	27 Participants n=7 Participants	23 Participants n=5 Participants	26 Participants n=4 Participants	103 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	36 participants n=5 Participants	36 participants n=7 Participants	33 participants n=5 Participants	37 participants n=4 Participants	142 participants n=21 Participants
Region of Enrollment Japan	36 participants n=5 Participants	36 participants n=7 Participants	39 participants n=5 Participants	39 participants n=4 Participants	150 participants n=21 Participants
Height	165.6 cm STANDARD_DEVIATION 10.63 • n=5 Participants	165.7 cm STANDARD_DEVIATION 9.25 • n=7 Participants	165.8 cm STANDARD_DEVIATION 9.03 • n=5 Participants	166.0 cm STANDARD_DEVIATION 10.33 • n=4 Participants	165.8 cm STANDARD_DEVIATION 9.79 • n=21 Participants
Body Weight	78.72 kg STANDARD_DEVIATION 19.747 • n=5 Participants	80.52 kg STANDARD_DEVIATION 18.977 • n=7 Participants	78.39 kg STANDARD_DEVIATION 17.589 • n=5 Participants	78.84 kg STANDARD_DEVIATION 16.740 • n=4 Participants	79.11 kg STANDARD_DEVIATION 18.204 • n=21 Participants
BMI	28.54 kg/m^2 STANDARD_DEVIATION 5.535 • n=5 Participants	29.10 kg/m^2 STANDARD_DEVIATION 5.211 • n=7 Participants	28.35 kg/m^2 STANDARD_DEVIATION 4.978 • n=5 Participants	28.49 kg/m^2 STANDARD_DEVIATION 5.010 • n=4 Participants	28.62 kg/m^2 STANDARD_DEVIATION 5.167 • n=21 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Subjects who were randomized, took at least one dose of double-blind study medication, and had at least one post-randomization HbA1c measurement were included in the full analysis dataset (FAS). TheHbA1c change from baseline through 12 weeks, and the primary analysis is based on the available data and data obtained after rescue will be excluded and considered missing.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=65 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=68 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=68 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Change in HbA1c After 12 Weeks of Treatment	0.24 percentage of glycated hemoglobin Standard Error 0.08	-0.31 percentage of glycated hemoglobin Standard Error 0.08	-0.44 percentage of glycated hemoglobin Standard Error 0.08	-0.56 percentage of glycated hemoglobin Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline to up to 12 weeks

Population: Subjects with at least one post-baseline HbA1c value \<7% met this endpoint. HbA1c values obtained after start of rescue medication were excluded from this analysis. The number and percentage of subjects with at least one HbA1c value \<7% were summarized by treatment group for the FAS.

To assess the efficacy of bexagliflozin based on the proportion of subjects who reach the American Diabetes Associate (ADA) and the Japan Diabetes Society target HbA1c of \<7%.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=71 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=75 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Proportion of Subjects With HbA1c < 7%	11 Participants	15 Participants	16 Participants	27 Participants

SECONDARY outcome

Timeframe: Baseline to Week 2, Week 6 and Week 12

Population: Only subject with a value at the specified time is included

The body weight was analyzed on the full analysis set using the MMRM ANCOVA model used for the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=71 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=75 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Change in Body Weight Over Time Week 2	0.00 kg Standard Error 0.15	-0.74 kg Standard Error 0.16	-0.76 kg Standard Error 0.15	-0.99 kg Standard Error 0.15
Change in Body Weight Over Time Week 6	0.02 kg Standard Error 0.19	-1.00 kg Standard Error 0.19	-1.42 kg Standard Error 0.19	-1.49 kg Standard Error 0.19
Change in Body Weight Over Time Week 12	-0.14 kg Standard Error 0.25	-1.58 kg Standard Error 0.25	-1.72 kg Standard Error 0.25	-1.89 kg Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline to Week 2, Week 6 and Week 12

Population: Only subject with a value at the specified time is included

The fasting plasma glucose (FPG) was analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=71 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=75 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Change in Fasting Plasma Glucose (FPG) Over Time Week 2	-0.07 mmol/L Standard Error 0.16	-0.55 mmol/L Standard Error 0.16	-0.97 mmol/L Standard Error 0.16	-1.11 mmol/L Standard Error 0.15
Change in Fasting Plasma Glucose (FPG) Over Time Week 6	0.11 mmol/L Standard Error 0.17	-0.82 mmol/L Standard Error 0.17	-1.06 mmol/L Standard Error 0.17	-0.99 mmol/L Standard Error 0.17
Change in Fasting Plasma Glucose (FPG) Over Time Week 12	-0.11 mmol/L Standard Error 0.17	-0.96 mmol/L Standard Error 0.17	-1.16 mmol/L Standard Error 0.17	-1.18 mmol/L Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline to Week 2, Week 6 and Week 12

Population: Only subject with a value at the specified time is included

The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed on the full analysis set using the same MMRM ANCOVA model used in the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=71 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=75 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Change in Systolic and Diastolic Blood Pressure Over Time Week 12 DBP	0.81 mm Hg Standard Error 0.95	-1.43 mm Hg Standard Error 0.95	-0.66 mm Hg Standard Error 0.94	-1.23 mm Hg Standard Error 0.94
Change in Systolic and Diastolic Blood Pressure Over Time Week 2 SBP	-0.14 mm Hg Standard Error 1.42	-0.33 mm Hg Standard Error 1.43	-2.55 mm Hg Standard Error 1.42	-4.39 mm Hg Standard Error 1.38
Change in Systolic and Diastolic Blood Pressure Over Time Week 2 DBP	0.15 mm Hg Standard Error 0.89	-0.03 mm Hg Standard Error 0.89	-1.59 mm Hg Standard Error 0.88	-2.00 mm Hg Standard Error 0.86
Change in Systolic and Diastolic Blood Pressure Over Time Week 6 SBP	-0.57 mm Hg Standard Error 1.44	-1.40 mm Hg Standard Error 1.45	-3.96 mm Hg Standard Error 1.44	-3.07 mm Hg Standard Error 1.39
Change in Systolic and Diastolic Blood Pressure Over Time Week 6 DBP	-0.52 mm Hg Standard Error 0.92	-0.27 mm Hg Standard Error 0.93	-1.54 mm Hg Standard Error 0.92	-0.36 mm Hg Standard Error 0.89
Change in Systolic and Diastolic Blood Pressure Over Time Week 12 SBP	1.10 mm Hg Standard Error 1.56	-1.06 mm Hg Standard Error 1.57	-3.30 mm Hg Standard Error 1.55	-2.73 mm Hg Standard Error 1.55

SECONDARY outcome

Timeframe: Baseline to Week 2, Week 6 and Week 12

Population: Only subject with a value at the specified time is included

The least square mean (LSM) change from baseline to Week 2, Week 6 and Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes. The LSM change was calculated by excluding HbA1c data obtained after rescue medication.

Outcome measures

Outcome measures
Measure	Placebo n=72 Participants Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=71 Participants Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 Participants Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=75 Participants Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Change in HbA1c Over Time Week 2	-0.00 percentage of HbA1c Standard Error 0.04	-0.09 percentage of HbA1c Standard Error 0.04	-0.13 percentage of HbA1c Standard Error 0.04	-0.13 percentage of HbA1c Standard Error 0.04
Change in HbA1c Over Time Week 6	0.13 percentage of HbA1c Standard Error 0.06	-0.32 percentage of HbA1c Standard Error 0.06	-0.36 percentage of HbA1c Standard Error 0.06	-0.40 percentage of HbA1c Standard Error 0.06
Change in HbA1c Over Time Week 12	0.24 percentage of HbA1c Standard Error 0.08	-0.31 percentage of HbA1c Standard Error 0.08	-0.44 percentage of HbA1c Standard Error 0.08	-0.56 percentage of HbA1c Standard Error 0.08

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Bexagliflozin 5 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Bexagliflozin 10 mg

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Bexagliflozin 20 mg

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=72 participants at risk Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=72 participants at risk Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 participants at risk Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=76 participants at risk Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Cardiac disorders Acute myocardial infarction	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Hepatobiliary disorders Bile duct stone	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Infections and infestations Urinary Tract Infection	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.3% 1/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastroesophageal cancer	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.3% 1/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)

Other adverse events

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator has no publication right.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=72 participants at risk Placebo tablet once daily before breakfast Placebo tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 5 mg n=72 participants at risk Bexagliflozin tablet, 5 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 10 mg n=72 participants at risk Bexagliflozin tablet, 10 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.	Bexagliflozin 20 mg n=76 participants at risk Bexagliflozin tablet, 20 mg, once daily before breakfast Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Infections and infestations Nasopharyngitis	4.2% 3/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	6.9% 5/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	5.6% 4/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	3.9% 3/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Infections and infestations Pharyngitis	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	4.2% 3/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Infections and infestations Urinary tract infection	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.3% 1/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Infections and infestations Upper respiratory tract infection	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Renal and urinary disorders Dysuria	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	3.9% 3/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Renal and urinary disorders Polyuria	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	3.9% 3/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Renal and urinary disorders Pollakiuria	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.6% 2/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Musculoskeletal and connective tissue disorders Muscle spasms	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.3% 1/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.3% 1/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Nervous system disorders Dizziness	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Nervous system disorders Headache	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.6% 2/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Gastrointestinal disorders Nausea	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Gastrointestinal disorders Diarrhea	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Metabolism and nutrition disorders Hypoglycemia	1.4% 1/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	5.3% 4/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Eye disorders Vision blurred	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.8% 2/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
General disorders Thirst	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.6% 2/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.6% 2/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)
Reproductive system and breast disorders Balanoposthitis	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	0.00% 0/72 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)	2.6% 2/76 • Adverse event data were collected from Week -12 (S2, Washout period) to Week 14 (V5, Follow up period)