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

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 2; Hypertension
• Interventions: Drug: Placebo to Ertuglilflozin 1 or 5 mg; Drug: Ertugliflozin 1 mg; Drug: Ertugliflozin 5 mg; Drug: Placebo to HCTZ; Drug: Ertugliflozin 25 mg; Drug: HCTZ 12.5mg; Drug: Placebo to ertuglilflozin 25 mg

• Registration Number: NCT01096667
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

MK-8835-042 (B1521004) is designed to assess the safety and efficacy of an investigational drug, ertugliflozin (MK-8835, PF-04971729), in participants with type 2 diabetes and hypertension. Participants in the study will receive 1 of 5 treatments for 28 days (either placebo, 1 of 3 doses of ertugliflozin \[1, 5, or 25 mg\], or the approved drug hydrochlorothiazide \[HCTZ\]). The primary hypothesis of the study was that ertugliflozin was superior to placebo on the change from baseline in average, 24-hour systolic blood pressure (SBP) on Day 28.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-03-26
• Study First Submitted QC: 2010-03-30
• Study First Posted: 2010-03-31
• Study Start: 2010-05-17
• Primary Completion: 2011-02-09
• Study Completion: 2011-02-25
• Disposition First Submitted: 2013-04-10
• Disposition First Submitted QC: 2013-04-10
• Disposition First Posted: 2013-04-16
• Results First Submitted: 2017-11-15
• Results First Submitted QC: 2017-11-15
• Results First Posted: 2017-12-13
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-15
• Last Update Posted: 2018-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 194

Inclusion Criteria

• Participants with type 2 diabetes and hypertension
• Medically stable
• On at least 1 (and up to 2) oral diabetes drugs
• And up to 2 medicines for blood pressure control

Exclusion Criteria

• Participants with type 1 diabetes
• Heart attack
• Stroke
• Uncontrolled blood pressure
• Significant kidney disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo to Ertuglilflozin 1 or 5 mg	Placebo to ertugliflozin (resembling either 1 mg or 5 mg), placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days.
Placebo	Placebo to HCTZ	Placebo to ertugliflozin (resembling either 1 mg or 5 mg), placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days.
Placebo	Placebo to ertuglilflozin 25 mg	Placebo to ertugliflozin (resembling either 1 mg or 5 mg), placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days.
Ertugliflozin 1 mg	Ertugliflozin 1 mg	Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 1 mg	Placebo to HCTZ	Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 1 mg	Placebo to ertuglilflozin 25 mg	Ertugliflozin 1 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 5 mg	Ertugliflozin 5 mg	Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 25 mg	Placebo to Ertuglilflozin 1 or 5 mg	Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 25 mg	Ertugliflozin 25 mg	Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 25 mg	Placebo to HCTZ	Ertugliflozin 25 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 5 mg	Placebo to HCTZ	Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
Ertugliflozin 5 mg	Placebo to ertuglilflozin 25 mg	Ertugliflozin 5 mg, placebo to ertugliflozin (resembling 25 mg), and placebo to HCTZ once daily for 28 days
HCTZ 12.5mg	HCTZ 12.5mg	HCTZ 12.5 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to ertugliflozin (resembling 25 mg) once daily for 28 days
HCTZ 12.5mg	Placebo to Ertuglilflozin 1 or 5 mg	HCTZ 12.5 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to ertugliflozin (resembling 25 mg) once daily for 28 days
HCTZ 12.5mg	Placebo to ertuglilflozin 25 mg	HCTZ 12.5 mg, placebo to ertugliflozin (resembling either 1 mg or 5 mg), and placebo to ertugliflozin (resembling 25 mg) once daily for 28 days

Primary Outcome Measures

Name	Time	Method
Baseline 24-hour Average Systolic Blood Pressure (SBP)	24 hours	Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).
Change From Baseline on 24-hour Average SBP at Week 4	Baseline and Week 4	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Seated, Triplicate Trough SBP at Week 4	Baseline and Week 4	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.
Baseline Average Daytime and Nighttime SBP	Daytime: 16 hours; Nighttime: 8 hours	Daytime was defined as 0600 to 2159 hours, inclusive, local time. Nighttime was defined as 2200 to 0559 hours, inclusive, local time.
Change From Baseline on Daytime Average SBP at Week 4	Baseline and Week 4	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.
Change From Baseline on Nighttime Average SBP at Week 4	Baseline and Week 4	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.
Baseline Seated, Triplicate Trough SBP	Baseline	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.
Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (DBP)	up to 24 hours	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.
Change From Baseline on Daytime Average DBP at Week 4	Baseline and Week 4	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.
Change From Baseline on Nighttime Average DBP at Week 4	Baseline and Week 4	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.
Baseline Seated, Triplicate Trough DBP	Baseline	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.
Change From Baseline in Seated, Triplicate Trough DBP at Week 4	Baseline and Week 4	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.
Change From Baseline on 24-hour Average DBP at Week 4	Baseline and Week 4	Change from baseline on 24-hour average DBP at Week 4 using 24 hour ABPM. In the case of missing data, LOCF.
Baseline 24-hour, Daytime and Nightime Average Heart Rate	up to 24 hours	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.
Change From Baseline on 24-hour Average Heart Rate at Week 4	Baseline and Week 4	Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM.
Change From Baseline on Daytime Average Heart Rate at Week 4	Baseline and Week 4	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.
Change From Baseline on Nighttime Average Heart Rate at Week 4	Baseline and Week 4	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.
Baseline Seated, Triplicate Trough Heart Rate	Baseline	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.
Change From Baseline in Seated, Triplicate Trough Heart Rate at Week 4	Baseline and Week 4	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.
Baseline 24-hour Average Urinary Glucose Excretion	24 hours	Urinary glucose excetion was corrected for a duration of 24 hours (with appropriate duration of collection defined as \>20 hours and \<28 hours).
Change From Baseline on 24-hour Urinary Glucose Excretion at Week 4	Baseline and Week 4	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.
Baseline Fasting Plasma Glucose (FPG)	Baseline	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
Change From Baseline in FPG at Week 4	Baseline and Week 4	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
Change From Baseline in FPG at Week 2	Baseline and Week 2	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).
Number of Participants Who Experienced an Adverse Event (AE)	Up to 63 days (including run-in, treatment period, and follow-up)	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.
Number of Participants Who Discontinued Study Drug Due to an AE	Up to 28 days (treatment period)	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.