Trial Outcomes & Findings for An Integrated Assessment of the Safety and Effectiveness of Bexagliflozin for the Management of Essential Hypertension (NCT NCT03514641)

NCT ID: NCT03514641

Last Updated: 2021-09-21

Results Overview

Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

673 participants

Primary outcome timeframe

Baseline (Day 1) to week 12

Results posted on

2021-09-21

Participant Flow

In the first part of the study (603A), the subjects were randomized to receive bexagliflozin or placebo for 12 weeks.

Participant milestones

Participant milestones
Measure	603A: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks	603A: Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for 12 weeks.	603B: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks from week 24 to week 36 (cumulative)	603B: Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for 12 weeks from week 24 to week 36 (cumulative)
603A: 0-12 Week Study Period STARTED	334	339	0	0
603A: 0-12 Week Study Period COMPLETED	307	319	0	0
603A: 0-12 Week Study Period NOT COMPLETED	27	20	0	0
603B: 24-36 Week Study Period STARTED	0	0	281	281
603B: 24-36 Week Study Period COMPLETED	0	0	267	266
603B: 24-36 Week Study Period NOT COMPLETED	0	0	14	15

Reasons for withdrawal

Reasons for withdrawal
Measure	603A: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks	603A: Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for 12 weeks.	603B: Bexagliflozin Tablets, 20 mg Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks from week 24 to week 36 (cumulative)	603B: Placebo Tablets Each subject will receive placebo (inactive tablet) once daily for 12 weeks from week 24 to week 36 (cumulative)
603A: 0-12 Week Study Period Protocol Violation	3	3	0	0
603A: 0-12 Week Study Period Adverse Event	5	2	0	0
603A: 0-12 Week Study Period Withdrawal by Subject	7	5	0	0
603A: 0-12 Week Study Period Lost to Follow-up	10	9	0	0
603A: 0-12 Week Study Period Physician Decision	1	0	0	0
603A: 0-12 Week Study Period Lack of Efficacy	1	0	0	0
603A: 0-12 Week Study Period 24 hr ABPM not enough readings	0	1	0	0
603B: 24-36 Week Study Period Protocol Violation	0	0	0	2
603B: 24-36 Week Study Period Adverse Event	0	0	3	1
603B: 24-36 Week Study Period Withdrawal by Subject	0	0	2	3
603B: 24-36 Week Study Period Lost to Follow-up	0	0	6	6
603B: 24-36 Week Study Period 24 hr ABPM not enough readings	0	0	3	3

Baseline Characteristics

First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	603A: Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	603 A: Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.	603B: Bexagliflozin Tablets, 20 mg n=281 Participants Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	603B: Placebo Tablets n=281 Participants Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive placebo (inactive tablets) once daily for 12 weeks.	Total n=1235 Participants Total of all reporting groups
Age, Continuous 603A: 0-12 Week Study Period	59.4 years STANDARD_DEVIATION 11.32 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	58.3 years STANDARD_DEVIATION 12.06 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	58.9 years STANDARD_DEVIATION 11.71 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Age, Continuous 603B: 12-36 Week Study Period	—	—	59.9 years STANDARD_DEVIATION 11.39 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	59.2 years STANDARD_DEVIATION 11.78 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	59.6 years STANDARD_DEVIATION 11.58 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Sex: Female, Male 603A: 0-12 Week Study Period · Female	127 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	139 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	266 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Sex: Female, Male 603A: 0-12 Week Study Period · Male	207 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	200 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	407 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Sex: Female, Male 603B: 12-36 Week Study Period · Female	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	110 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	114 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	224 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Sex: Female, Male 603B: 12-36 Week Study Period · Male	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	171 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	167 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	338 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period · Hispanic or Latino	27 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	27 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	54 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period · Not Hispanic or Latino	307 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	312 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	619 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603A: 0-12 Week Study Period · Unknown or Not Reported	0 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period · Hispanic or Latino	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	27 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	19 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	46 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period · Not Hispanic or Latino	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	254 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	262 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	516 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ethnicity (NIH/OMB) 603B: 12-36 Week Study Period · Unknown or Not Reported	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · American Indian or Alaska Native	0 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	2 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	2 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · Asian	7 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	4 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	11 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · Native Hawaiian or Other Pacific Islander	1 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	1 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · Black or African American	94 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	104 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	198 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · White	219 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	220 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	439 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · More than one race	4 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	3 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	7 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603A: 0-12 Week Study Period · Unknown or Not Reported	9 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	6 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	15 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · American Indian or Alaska Native	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	1 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	1 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	2 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · Asian	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	4 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	4 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	8 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · Native Hawaiian or Other Pacific Islander	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · Black or African American	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	92 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	70 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	162 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · White	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	178 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	195 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	373 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · More than one race	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	2 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	4 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	6 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Race (NIH/OMB) 603B: 12-36 Week Study Period · Unknown or Not Reported	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	0 Participants First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	4 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	7 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	11 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Body Mass Index 603A: 0-12 Week Study Period	32.29 kg/m^2 STANDARD_DEVIATION 6.522 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	32.90 kg/m^2 STANDARD_DEVIATION 6.527 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	32.59 kg/m^2 STANDARD_DEVIATION 6.527 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Body Mass Index 603B: 12-36 Week Study Period	—	—	32.22 kg/m^2 STANDARD_DEVIATION 6.952 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	33.17 kg/m^2 STANDARD_DEVIATION 6.144 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	32.69 kg/m^2 STANDARD_DEVIATION 6.572 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Body Weight at Baseline 603A: 0-12 Week Study Period	95.36 kg STANDARD_DEVIATION 22.643 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	97.47 kg STANDARD_DEVIATION 22.673 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	96.42 kg STANDARD_DEVIATION 22.666 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Body Weight at Baseline 603B: 12-36 Week Study Period	—	—	95.71 kg STANDARD_DEVIATION 24.321 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	97.55 kg STANDARD_DEVIATION 21.003 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	96.63 kg STANDARD_DEVIATION 22.721 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
History of Diabetes 603A: 0-12 Week Study Period · Yes	83 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	84 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	167 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
History of Diabetes 603A: 0-12 Week Study Period · No	251 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	255 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	506 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
History of Diabetes 603B: 12-36 Week Study Period · Yes	—	—	78 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	66 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	144 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
History of Diabetes 603B: 12-36 Week Study Period · No	—	—	203 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	215 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	418 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Use of any antihypertension medication 603A: 0-12 Week Study Period	269 Participants n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	276 Participants n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	545 Participants n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Use of any antihypertension medication 603B: 12-36 Week Study Period	—	—	233 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	226 Participants n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	459 Participants n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Estimated Glomerular Filtration Rate (eGFR) Mean 603A: 0-12 Week Study Period	82.64 mL/min/1.73 m^2 STANDARD_DEVIATION 17.438 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	84.42 mL/min/1.73 m^2 STANDARD_DEVIATION 19.710 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	83.53 mL/min/1.73 m^2 STANDARD_DEVIATION 18.625 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Estimated Glomerular Filtration Rate (eGFR) Mean 603B: 12-36 Week Study Period	—	—	78.75 mL/min/1.73 m^2 STANDARD_DEVIATION 18.971 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	77.95 mL/min/1.73 m^2 STANDARD_DEVIATION 18.871 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	78.35 mL/min/1.73 m^2 STANDARD_DEVIATION 18.908 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603A: 0-12 Week Study Period; SBP	147.58 mm Hg STANDARD_DEVIATION 9.640 • n=329 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	147.48 mm Hg STANDARD_DEVIATION 10.064 • n=339 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	—	—	147.53 mm Hg STANDARD_DEVIATION 9.850 • n=668 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.
Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603A: 0-12 Week Study Period; DBP	85.04 mm Hg STANDARD_DEVIATION 9.240 • n=329 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	84.97 mm Hg STANDARD_DEVIATION 10.216 • n=339 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	—	—	85.01 mm Hg STANDARD_DEVIATION 9.740 • n=668 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.
Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603B: 12-36 Week Study Period; SBP	—	—	136.30 mm Hg STANDARD_DEVIATION 13.844 • n=281 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	135.62 mm Hg STANDARD_DEVIATION 13.510 • n=281 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	135.96 mm Hg STANDARD_DEVIATION 13.67 • n=562 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.
Ambulatory Blood Pressure Monitoring (ABPM) at baseline 603B: 12-36 Week Study Period; DBP	—	—	79.58 mm Hg STANDARD_DEVIATION 10.471 • n=281 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	79.20 mm Hg STANDARD_DEVIATION 10.571 • n=281 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.	79.39 mm Hg STANDARD_DEVIATION 10.513 • n=562 Participants • Subjects who experienced worsening of their hypertension prior to the 6-week visit were not to undergo ABPM measurement.
Office seated SBP and DBP at baseline 603A: 0-12 Week Study Period; SBP	156.44 mm Hg STANDARD_DEVIATION 10.513 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	155.84 mm Hg STANDARD_DEVIATION 10.335 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	156.14 mm Hg STANDARD_DEVIATION 10.420 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Office seated SBP and DBP at baseline 603A: 0-12 Week Study Period; DBP	91.29 mm Hg STANDARD_DEVIATION 10.269 • n=334 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	91.48 mm Hg STANDARD_DEVIATION 10.619 • n=339 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	—	—	91.39 mm Hg STANDARD_DEVIATION 10.439 • n=673 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Office seated SBP and DBP at baseline 603B: 12-36 Week Study Period; SBP	—	—	141.18 mm Hg STANDARD_DEVIATION 16.231 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	140.69 mm Hg STANDARD_DEVIATION 14.960 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	140.94 mm Hg STANDARD_DEVIATION 15.596 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.
Office seated SBP and DBP at baseline 603B: 12-36 Week Study Period; DBP	—	—	84.75 mm Hg STANDARD_DEVIATION 11.623 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	85.28 mm Hg STANDARD_DEVIATION 11.588 • n=281 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.	84.55 mm Hg STANDARD_DEVIATION 10.985 • n=562 Participants • First row corresponds to participants only in 603A. Second row corresponds to participants only in 603B.

PRIMARY outcome

Timeframe: Baseline (Day 1) to week 12

Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared to placebo

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
Change of the 24 Hour Mean Systolic Blood Pressure From Baseline (Day 1) to Week 12	-8.86 mm Hg Standard Error 0.642	-6.15 mm Hg Standard Error 0.622

PRIMARY outcome

Timeframe: Change from week 24 to week 36

Change of the 24 hour mean systolic blood pressure in the bexagliflozin group compared placebo

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=281 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=281 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
Change of the 24 Hour Mean Systolic Blood Pressure From Cumulative Week 24 to Week 36	0.30 mm Hg Standard Error 0.680	2.74 mm Hg Standard Error 0.678

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline 24-hour mean SBP/DBP value as a fixed effect covariate.

Proportion of subjects who achieve a reduction of mean ambulatory systolic blood pressure of 10 mm Hg or greater

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Reduction of Mean Ambulatory Systolic Blood Pressure	0.40 proportion of participants Interval 0.35 to 0.46	0.34 proportion of participants Interval 0.29 to 0.4

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Proportion of subjects who achieve a mean ambulatory systolic blood pressure of 135 mm Hg or less

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Mean Ambulatory Systolic Blood Pressure of 135 mm Hg or Less	0.40 Proportion of subjects Interval 0.34 to 0.46	0.29 Proportion of subjects Interval 0.24 to 0.35

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Placebo-adjusted change in seated office systolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Change in Seated Office Systolic Blood Pressure	-11.24 mm Hg Standard Error 0.799	-6.61 mm Hg Standard Error 0.787

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Population: The full model is a logistic regression that includes diabetes status (history of type 2 diabetes mellitus or not), eGFR at screening, pre-treatment status (presently medicated for hypertension or not), treatment, and the baseline seated office SBP/DBP value as a fixed effect covariate.

Proportion of subjects who achieve a seated office systolic blood pressure of 140 mm Hg or less

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Seated Office Systolic Blood Pressure of 140 mm Hg or Less	0.38 Proportion of subjects Interval 0.33 to 0.44	0.25 Proportion of subjects Interval 0.21 to 0.3

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Placebo-adjusted change in mean ambulatory diastolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Change in Mean Ambulatory Diastolic Blood Pressure	-3.92 mm Hg Standard Error 0.349	-3.08 mm Hg Standard Error 0.337

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Proportion of subjects who achieve a mean ambulatory diastolic blood pressure of 87 mm Hg or less

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Mean Ambulatory Diastolic Blood Pressure of 87 mm Hg or Less	0.47 Proportion of subjects Interval 0.41 to 0.53	0.37 Proportion of subjects Interval 0.32 to 0.43

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Proportion of subjects who achieve a reduction of mean ambulatory diastolic blood pressure of 4 mm Hg or greater

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Reduction of Mean Ambulatory Diastolic Blood Pressure of 4 mm Hg or Greater	0.88 Proportion of subjects Interval 0.83 to 0.92	0.80 Proportion of subjects Interval 0.73 to 0.85

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Placebo-adjusted change in seated office diastolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Change in Seated Office Diastolic Blood Pressure	-4.44 mm Hg Standard Error 0.504	-2.13 mm Hg Standard Error 0.496

SECONDARY outcome

Timeframe: Baseline (Day 1) to week 12

Proportion of subjects who achieve a mean seated office diastolic blood pressure of 90 mm Hg or less

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=334 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=339 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603A, Seated Office Diastolic Blood Pressure of 90 mm Hg or Less	0.65 Proportion of subjects Interval 0.59 to 0.71	0.53 Proportion of subjects Interval 0.47 to 0.59

SECONDARY outcome

Timeframe: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)

Placebo-adjusted change from week 12 to week 24 in seated office systolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=281 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=281 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603B, Change in Seated Office Systolic Blood Pressure	1.98 mm Hg Standard Error 0.846	5.18 mm Hg Standard Error 0.859

SECONDARY outcome

Timeframe: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)

Placebo-adjusted change in mean ambulatory diastolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=281 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=281 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603B, Change in Mean Ambulatory Diastolic Blood Pressure	0.10 mm Hg Standard Error 0.369	0.94 mm Hg Standard Error 0.368

SECONDARY outcome

Timeframe: Week 12 (cumulative week 24) to Week 24 (cumulative week 36)

Placebo-adjusted change from week 12 to week 24 in seated office diastolic blood pressure

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=281 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=281 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
603B, Change in Seated Office Diastolic Blood Pressure	0.51 mm Hg Standard Error 0.507	1.76 mm Hg Standard Error 0.514

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1) to cumulative week 36

Population: Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin

Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on mean ambulatory systolic and diastolic blood pressure after 12 weeks of bexagliflozin treatment, as well as longer treatment periods, i.e., 24 weeks or 36 weeks of bexagliflozin treatment.

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=649 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=649 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure 12 Weeks	-7.595 mm Hg Interval -8.565 to -6.625	-3.269 mm Hg Interval -3.773 to -2.764
Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure 24 Weeks	-9.262 mm Hg Interval -10.559 to -7.965	-4.044 mm Hg Interval -4.72 to -3.368
Integrated 603A and 603B, Effects on Mean Ambulatory Systolic and Diastolic Blood Pressure 36 Weeks	-12.454 mm Hg Interval -14.988 to -9.921	-5.566 mm Hg Interval -6.825 to -4.308

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1) to cumulative week 36

Population: Number of subjects with baseline and value after specified weeks of exposure to Bexagliflozin

Integration of measures collected in studies 603A and 603B will be used to assess consistent effects on seated office systolic and diastolic blood pressure over time

Outcome measures

Outcome measures
Measure	Bexagliflozin Tablets, 20 mg n=649 Participants Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	Placebo Tablets n=649 Participants Each subject will receive placebo (inactive tablet) once daily for 12 weeks.
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure 6 Weeks	-8.43 mm Hg Standard Deviation 16.399	-4.50 mm Hg Standard Deviation 9.534
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure 12 Weeks	-9.91 mm Hg Standard Deviation 15.777	-4.10 mm Hg Standard Deviation 9.716
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure 18 Weeks	-14.46 mm Hg Standard Deviation 16.000	-5.87 mm Hg Standard Deviation 9.282
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure 24 Weeks	-12.53 mm Hg Standard Deviation 18.830	-4.92 mm Hg Standard Deviation 10.910
Integrated 603A and 603B, Effects on Seated Office Systolic and Diastolic Blood Pressure 36 Weeks	-15.71 mm Hg Standard Deviation 16.975	-6.47 mm Hg Standard Deviation 9.933

Adverse Events

603A: Bexagliflozin Tablets, 20 mg

Serious events: 11 serious events

Other events: 94 other events

Deaths: 0 deaths

603A: Placebo Tablets

Serious events: 10 serious events

Other events: 88 other events

Deaths: 0 deaths

603B: Bexagliflozin Tablets, 20 mg

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

603B: Placebo Tablets

Serious events: 6 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 688-4221

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator has no right to publish the study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	603A: Bexagliflozin Tablets, 20 mg n=334 participants at risk Each subject will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	603A: Placebo Tablets n=339 participants at risk Each subject will receive placebo (inactive tablet) once daily for 12 weeks.	603B: Bexagliflozin Tablets, 20 mg n=281 participants at risk Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive bexagliflozin tablets, 20 mg once daily for 12 weeks.	603B: Placebo Tablets n=281 participants at risk Each eligible subject who have completed 603A including two successful 24-h ABPM sessions at 603A baseline and at week 12, and have completed the 12 weeks open labeled bexagliflozin run-in period with a successful 24-h ABPM session at week 12 of 603B, will receive placebo tablets (inactive), 20 mg once daily for 12 weeks.
Gastrointestinal disorders Abdominal pain	0.60% 2/334 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.59% 2/339 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Gastrointestinal disorders Constipation	1.8% 6/334 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.88% 3/339 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Gastrointestinal disorders Diarrhoea	1.2% 4/334 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Gastrointestinal disorders Dry mouth	1.2% 4/334 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.59% 2/339 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Gastrointestinal disorders Nausea	2.1% 7/334 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Gastrointestinal disorders Vomiting	0.90% 3/334 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.8% 6/339 • Number of events 6 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
General disorders Oedema peripheral	0.90% 3/334 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.1% 7/339 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Bronchitis	0.60% 2/334 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Gastroenteritis	0.90% 3/334 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.29% 1/339 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Genital infection fungal	1.2% 4/334 • Number of events 8 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/339 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Influenza	1.5% 5/334 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.88% 3/339 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Nasopharyngitis	3.6% 12/334 • Number of events 12 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	3.2% 11/339 • Number of events 11 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.4% 4/281 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Upper respiratory tract infection	1.5% 5/334 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.9% 10/339 • Number of events 11 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Infections and infestations Urinary tract infection	2.1% 7/334 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.1% 7/339 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.1% 6/281 • Number of events 6 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.1% 6/281 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Injury, poisoning and procedural complications Ligament sprain	1.8% 6/334 • Number of events 6 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/339 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Metabolism and nutrition disorders Polydipsia	0.90% 3/334 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Musculoskeletal and connective tissue disorders Arthralgia	0.60% 2/334 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Musculoskeletal and connective tissue disorders Back pain	1.5% 5/334 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.5% 5/339 • Number of events 5 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.30% 1/334 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.29% 1/339 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Musculoskeletal and connective tissue disorders Pain in extremity	0.60% 2/334 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.59% 2/339 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Nervous system disorders Dizziness	2.1% 7/334 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.29% 1/339 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Nervous system disorders Headache	1.2% 4/334 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.1% 7/339 • Number of events 7 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Renal and urinary disorders Pollakiuria	3.9% 13/334 • Number of events 13 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.2% 4/339 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.00% 0/281 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Renal and urinary disorders Polyuria	1.2% 4/334 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	2.7% 9/339 • Number of events 9 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 4/334 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.2% 4/339 • Number of events 4 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Skin and subcutaneous tissue disorders Rash	0.60% 2/334 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.88% 3/339 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.36% 1/281 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.1% 3/281 • Number of events 3 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.
Vascular disorders Hypertension	0.30% 1/334 • Number of events 1 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	1.8% 6/339 • Number of events 6 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.	0.71% 2/281 • Number of events 2 • For 603A, adverse events were collected from baseline to Week 12. For 603B, adverse events were collected from Week 24 to Week 36.