Trial Outcomes & Findings for Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042) (NCT NCT01096667)

Results Overview

Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

194 participants

Primary outcome timeframe

24 hours

Results posted on

2018-09-13

Participant Flow

Prior to randomization, 194 participants received placebo for at least 3 weeks (completed the run-in period). Treated participants included all randomized participants who received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Placebo Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to hydrochlorothiazide (HCTZ), once daily for 28 days.	Ertugliflozin 1 mg Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Overall Study STARTED	39	39	38	39	39
Overall Study Treated	38	39	38	39	39
Overall Study COMPLETED	36	37	36	36	39
Overall Study NOT COMPLETED	3	2	2	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to hydrochlorothiazide (HCTZ), once daily for 28 days.	Ertugliflozin 1 mg Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days
Overall Study Lost to Follow-up	1	1	1	0
Overall Study Withdrawal by Subject	1	0	0	1
Overall Study Reason not available	0	1	1	1
Overall Study Protocol Violation	0	0	0	1
Overall Study Not treated	1	0	0	0

Baseline Characteristics

Study of Safety and Efficacy Of Ertugliflozin (PF-04971729, MK-8835) In Participants With Type 2 Diabetes And Hypertension (MK-8835-042)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days	Total n=193 Participants Total of all reporting groups
Age, Customized <18 years	0 Participants n=85 Participants	0 Participants n=18 Participants	0 Participants n=39 Participants	0 Participants	0 Participants n=11 Participants	0 Participants n=19 Participants
Age, Customized Between 18 and 44 years	3 Participants n=85 Participants	4 Participants n=18 Participants	3 Participants n=39 Participants	5 Participants	1 Participants n=11 Participants	16 Participants n=19 Participants
Age, Customized Between 45 and 64 years	34 Participants n=85 Participants	34 Participants n=18 Participants	32 Participants n=39 Participants	34 Participants	34 Participants n=11 Participants	168 Participants n=19 Participants
Age, Customized 65 years and older	1 Participants n=85 Participants	1 Participants n=18 Participants	3 Participants n=39 Participants	0 Participants	4 Participants n=11 Participants	9 Participants n=19 Participants
Sex: Female, Male Female	14 Participants n=85 Participants	12 Participants n=18 Participants	13 Participants n=39 Participants	12 Participants	11 Participants n=11 Participants	62 Participants n=19 Participants
Sex: Female, Male Male	24 Participants n=85 Participants	27 Participants n=18 Participants	25 Participants n=39 Participants	27 Participants	28 Participants n=11 Participants	131 Participants n=19 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for average 24-hour SBP.

Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=38 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline 24-hour Average Systolic Blood Pressure (SBP)	136.11 mmHg Standard Deviation 15.298	133.13 mmHg Standard Deviation 10.868	135.08 mmHg Standard Deviation 12.073	135.59 mmHg Standard Deviation 11.929	139.55 mmHg Standard Deviation 11.941

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on 24-hour average SBP at Week 4 assessed using 24-hour ABPM. In the case of missing data, last observation carried forward (LOCF).

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on 24-hour Average SBP at Week 4	0.26 mmHg Interval -1.31 to 1.7	-2.71 mmHg Interval -4.15 to -1.33	-3.73 mmHg Interval -5.3 to -2.18	-3.42 mmHg Interval -4.86 to -1.99	-2.95 mmHg Interval -4.39 to -1.51

SECONDARY outcome

Timeframe: Daytime: 16 hours; Nighttime: 8 hours

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for daytime and nighttime SBP.

Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=38 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline Average Daytime and Nighttime SBP Daytime	139.95 mmHg Standard Deviation 15.107	136.85 mmHg Standard Deviation 11.361	138.89 mmHg Standard Deviation 11.724	139.56 mmHg Standard Deviation 12.343	143.32 mmHg Standard Deviation 12.637
Baseline Average Daytime and Nighttime SBP Nighttime	127.54 mmHg Standard Deviation 16.858	125.15 mmHg Standard Deviation 12.180	126.37 mmHg Standard Deviation 13.956	127.13 mmHg Standard Deviation 13.553	131.68 mmHg Standard Deviation 12.912

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on daytime average SBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Daytime Average SBP at Week 4	0.82 mmHg Interval -0.9 to 2.34	-2.88 mmHg Interval -4.49 to -1.44	-3.61 mmHg Interval -5.3 to -1.94	-4.17 mmHg Interval -5.72 to -2.63	-3.10 mmHg Interval -4.66 to -1.57

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on nighttime average SBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Nighttime Average SBP at Week 4	-0.29 mmHg Interval -2.28 to 1.71	-2.48 mmHg Interval -4.33 to -0.6	-3.47 mmHg Interval -5.53 to -1.39	-2.31 mmHg Interval -4.21 to -0.4	-2.30 mmHg Interval -4.2 to -0.4

SECONDARY outcome

Timeframe: Baseline

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for seated, triplicate, trough SBP.

Trough SBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. Baseline trough SBP is calculated as the mean of triplicate (3) trough SBP measures.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline Seated, Triplicate Trough SBP	135.17 mmHg Standard Deviation 14.183	134.23 mmHg Standard Deviation 13.631	137.31 mmHg Standard Deviation 14.834	135.25 mmHg Standard Deviation 13.452	138.07 mmHg Standard Deviation 12.958

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement for sitting, triplicate trough SBP.

Trough SBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=37 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=36 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=36 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline in Seated, Triplicate Trough SBP at Week 4	1.24 mmHg Interval -0.93 to 3.41	-2.77 mmHg Interval -4.95 to -0.6	-5.92 mmHg Interval -8.12 to -3.73	-4.96 mmHg Interval -7.15 to -2.77	-3.13 mmHg Interval -5.26 to -1.0

SECONDARY outcome

Timeframe: up to 24 hours

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for average 24-hour, daytime and nighttime DBP.

Baseline 24-hour average DBP was assessed using 24-hour ABPM. Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=38 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP) Nighttime	74.24 mmHg Standard Deviation 9.717	72.05 mmHg Standard Deviation 9.330	73.05 mmHg Standard Deviation 9.034	73.28 mmHg Standard Deviation 8.760	75.76 mmHg Standard Deviation 10.042
Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP) 24-hr	81.89 mmHg Standard Deviation 9.655	78.67 mmHg Standard Deviation 8.600	80.18 mmHg Standard Deviation 8.655	80.36 mmHg Standard Deviation 8.650	82.66 mmHg Standard Deviation 9.459
Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP) Daytime	85.32 mmHg Standard Deviation 10.127	81.77 mmHg Standard Deviation 8.925	83.47 mmHg Standard Deviation 9.164	83.59 mmHg Standard Deviation 9.295	85.87 mmHg Standard Deviation 9.884

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on 24-hour average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on 24-hour Average DBP at Week 4	0.77 mmHg Interval -0.25 to 1.75	-1.89 mmHg Interval -2.81 to -0.95	-2.34 mmHg Interval -3.37 to -1.31	-1.50 mmHg Interval -2.45 to -0.55	-1.42 mmHg Interval -2.37 to -0.48

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on daytime average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Daytime Average DBP at Week 4	0.87 mmHg Interval -0.24 to 1.85	-2.12 mmHg Interval -3.13 to -1.18	-1.88 mmHg Interval -2.96 to -0.8	-1.77 mmHg Interval -2.77 to -0.78	-1.69 mmHg Interval -2.67 to -0.7

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline on nighttime average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Nighttime Average DBP at Week 4	1.02 mmHg Interval -0.39 to 2.44	-1.48 mmHg Interval -2.78 to -0.15	-2.52 mmHg Interval -3.98 to -1.06	-0.84 mmHg Interval -2.19 to 0.51	-0.55 mmHg Interval -1.95 to 0.71

SECONDARY outcome

Timeframe: Baseline

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for seated, triplicate, trough DBP.

Trough DBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. Baseline trough DBP is calculated as the mean of triplicate (3) trough DBP measures.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline Seated, Triplicate Trough DBP	84.89 mmHg Standard Deviation 9.462	83.08 mmHg Standard Deviation 7.557	83.79 mmHg Standard Deviation 7.904	83.89 mmHg Standard Deviation 8.290	84.72 mmHg Standard Deviation 8.043

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement for sitting, triplicate trough DBP.

Trough DBP was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the blood pressure measure is obtained. Three measurements of blood pressure were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=37 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=36 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=36 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline in Seated, Triplicate Trough DBP at Week 4	0.30 mmHg Interval -0.97 to 1.58	-0.90 mmHg Interval -2.18 to 0.37	-0.75 mmHg Interval -2.03 to 0.54	-2.71 mmHg Interval -4.0 to -1.43	-2.54 mmHg Interval -3.79 to -1.29

SECONDARY outcome

Timeframe: up to 24 hours

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for average 24-hour, daytime and nighttime heart rate.

Baseline 24-hour average heart rate was assessed using 24-hour ABPM. Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=38 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline 24-hour, Daytime and Nightime Average Heart Rate Nighttime	74.05 beats per minute Standard Deviation 9.871	74.44 beats per minute Standard Deviation 8.133	73.16 beats per minute Standard Deviation 10.205	73.49 beats per minute Standard Deviation 10.034	73.03 beats per minute Standard Deviation 9.736
Baseline 24-hour, Daytime and Nightime Average Heart Rate 24-hr	81.11 beats per minute Standard Deviation 9.486	80.74 beats per minute Standard Deviation 6.950	79.68 beats per minute Standard Deviation 10.081	79.41 beats per minute Standard Deviation 9.063	79.08 beats per minute Standard Deviation 9.216
Baseline 24-hour, Daytime and Nightime Average Heart Rate Daytime	84.43 beats per minute Standard Deviation 9.743	83.74 beats per minute Standard Deviation 7.044	82.71 beats per minute Standard Deviation 10.405	82.18 beats per minute Standard Deviation 9.136	81.95 beats per minute Standard Deviation 9.470

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on 24-hour Average Heart Rate at Week 4	1.00 Beats per minute Interval -0.21 to 2.16	-1.22 Beats per minute Interval -2.45 to -0.25	1.07 Beats per minute Interval -0.16 to 2.29	-1.39 Beats per minute Interval -2.52 to -0.26	-0.56 Beats per minute Interval -1.68 to 0.56

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline in daytime average heart rate at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Daytime was defined as 0600 to 2159 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Daytime Average Heart Rate at Week 4	1.58 Beats per minute Interval 0.25 to 2.83	-1.80 Beats per minute Interval -3.09 to -0.7	1.10 Beats per minute Interval -0.24 to 2.43	-1.07 Beats per minute Interval -2.31 to 0.15	-0.06 Beats per minute Interval -1.22 to 1.22

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and a post-randomization measurement for average, 24-hour SBP.

Change from baseline in 24-hour nighttime average heart rate at Week 4 using 24 hour ABPM. In the case of missing data, LOCF. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=28 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=33 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=34 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on Nighttime Average Heart Rate at Week 4	-0.18 Beats per minute Interval -1.63 to 1.25	-0.15 Beats per minute Interval -1.76 to 0.91	1.43 Beats per minute Interval -0.07 to 2.92	-1.99 Beats per minute Interval -3.38 to -0.63	-1.24 Beats per minute Interval -2.7 to 0.0

SECONDARY outcome

Timeframe: Baseline

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for seated, triplicate, trough heart rate.

Trough heart rate was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the heart rate measure was obtained. Three measurements of heart rate were taken at least 2-minutes apart. Baseline trough heart rate is calculated as the mean of triplicate (3) trough heart rate measures.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline Seated, Triplicate Trough Heart Rate	77.07 beats per minute Standard Deviation 9.713	78.73 beats per minute Standard Deviation 8.446	77.30 beats per minute Standard Deviation 11.749	75.63 beats per minute Standard Deviation 9.550	77.97 beats per minute Standard Deviation 11.462

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement for sitting, triplicate trough heart rate.

Trough heart rate was measured using an automated blood pressure device with the participant in a seated position for at least 5 minutes before and while the heart rate measure was obtained. Three measurements of heart rate were taken at least 2-minutes apart. The change from baseline at Week 4 is the difference between the baseline and Week 4 assessments.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=37 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=36 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=36 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline in Seated, Triplicate Trough Heart Rate at Week 4	2.34 beats per minute Interval 0.85 to 3.82	-1.86 beats per minute Interval -3.35 to -0.38	1.22 beats per minute Interval -0.28 to 2.71	-1.51 beats per minute Interval -3.01 to -0.01	-0.99 beats per minute Interval -2.44 to 0.46

SECONDARY outcome

Timeframe: 24 hours

Population: All randomized participants who received at least one dose of study drug and had a baseline measurement for average urinary glucose excretion

Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as \>20 hours and \<28 hours).

Outcome measures

Outcome measures
Measure	Placebo n=36 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=38 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=37 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline 24-hour Average Urinary Glucose Excretion	13.35 grams/day Standard Deviation 22.913	9.97 grams/day Standard Deviation 20.085	8.04 grams/day Standard Deviation 13.135	17.56 grams/day Standard Deviation 29.101	6.96 grams/day Standard Deviation 8.562

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement for 24-hour urinary glucose excretion.

Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as \>20 hours and \<28 hours). In the case of missing data, LOCF.

Outcome measures

Outcome measures
Measure	Placebo n=35 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=36 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=34 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=36 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline on 24-hour Urinary Glucose Excretion at Week 4	4.15 grams/day Interval -3.5 to 11.81	46.33 grams/day Interval 38.79 to 53.88	64.54 grams/day Interval 56.77 to 72.31	74.49 grams/day Interval 66.87 to 82.11	-0.48 grams/day Interval -7.76 to 6.8

SECONDARY outcome

Timeframe: Baseline

Population: All randomized participants.

For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Baseline Fasting Plasma Glucose (FPG)	169.47 mg/dL Standard Deviation 51.073	158.38 mg/dL Standard Deviation 40.806	158.29 mg/dL Standard Deviation 42.465	172.03 mg/dL Standard Deviation 55.878	156.87 mg/dL Standard Deviation 36.541

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement at Week 4 for FPG (observed cases).

For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=36 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=35 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=35 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=37 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline in FPG at Week 4	4.39 mg/dL Interval -2.16 to 10.94	-13.70 mg/dL Interval -20.35 to -7.06	-30.41 mg/dL Interval -37.12 to -23.71	-31.03 mg/dL Interval -37.74 to -24.32	3.79 mg/dL Interval -2.74 to 10.31

SECONDARY outcome

Timeframe: Baseline and Week 2

Population: Analysis population consisted of all randomized participants who received at least 1 dose of blinded treatment and had baseline measurement and post-randomization measurement at Week 2 for FPG (observed cases).

For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=35 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=34 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=36 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=37 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Change From Baseline in FPG at Week 2	-5.44 mg/dL Interval -11.93 to 1.04	-10.98 mg/dL Interval -17.69 to -4.26	-22.45 mg/dL Interval -29.23 to -15.67	-32.03 mg/dL Interval -38.66 to -25.4	3.21 mg/dL Interval -3.32 to 9.74

SECONDARY outcome

Timeframe: Up to 63 days (including run-in, treatment period, and follow-up)

Population: Analysis population consisted of all randomized participants who received at least one dose of study drug.

An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. The table below includes all data collected since first dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Number of Participants Who Experienced an Adverse Event (AE)	9 Participants	8 Participants	15 Participants	12 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to 28 days (treatment period)

Population: Analysis population consisted of all randomized participants who received at least one dose of study drug.

An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. The table below includes all data collected since first dose of study drug. Discontinuation of study drug due to an AE includes temporary and permanent discontinuation of study drug due to an AE.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 Participants Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 Participants Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 Participants Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 Participants HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days
Number of Participants Who Discontinued Study Drug Due to an AE	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Ertugliflozin 1 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Ertugliflozin 5 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Ertugliflozin 25 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

HCTZ 12.5mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Pre-randomization

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=38 participants at risk Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 participants at risk Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 participants at risk Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 participants at risk Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 participants at risk HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days	Pre-randomization n=193 participants at risk；n=194 participants at risk Blinded placebo was administered for at least 21 days prior to randomization.
Injury, poisoning and procedural complications Extradural haematoma	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/194 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Injury, poisoning and procedural complications Skull fracture	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/194 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
General disorders Hematuria	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.52% 1/194 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).

Other adverse events

Other adverse events
Measure	Placebo n=38 participants at risk Placebo for Ertugliflozin (1 mg or 5 mg and 25 mg) and placebo to HCTZ, once daily for 28 days.	Ertugliflozin 1 mg n=39 participants at risk Ertugliflozin 1 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 5 mg n=38 participants at risk Ertugliflozin 5 mg, placebo to ertugliflozin (25 mg), and placebo to HCTZ, once daily for 28 days	Ertugliflozin 25 mg n=39 participants at risk Ertugliflozin 25 mg, placebo to ertugliflozin (1 mg or 5 mg), and placebo to HCTZ, once daily for 28 days	HCTZ 12.5mg n=39 participants at risk HCTZ 12.5 mg, placebo to ertugliflozin (1 mg or 5 mg and 25 mg), once daily for 28 days	Pre-randomization n=193 participants at risk；n=194 participants at risk Blinded placebo was administered for at least 21 days prior to randomization.
Nervous system disorders Dizziness	5.3% 2/38 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/39 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	1.6% 3/193 • Number of events 3 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Musculoskeletal and connective tissue disorders Athralgia	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.3% 2/38 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	1.0% 2/193 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
General disorders Fatigue	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
General disorders Pyrexia	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Infections and infestations Genital infection fungal	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	7.9% 3/38 • Number of events 3 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/39 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Infections and infestations Nasopharyngitis	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.3% 2/38 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Infections and infestations Upper respiratory tract infection	5.3% 2/38 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/39 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	1.6% 3/193 • Number of events 3 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Infections and infestations Urinary tract infection	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/39 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.3% 2/38 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/39 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.52% 1/193 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Nervous system disorders Headache	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.6% 1/38 • Number of events 1 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	2.1% 4/193 • Number of events 4 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).
Renal and urinary disorders Polyuria	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/38 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	5.1% 2/39 • Number of events 2 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/39 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).	0.00% 0/193 • Up to 63 days (including screening and run-in [pre-randomization], treatment period, and follow-up) Serious adverse events include all randomized participants who received at least one dose of study drug except for the pre-randomization arm that includes all randomized participants. Non-serious adverse events include all randomized participants who received at least one dose of study drug (all arms).

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to the sponsor at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER