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

Hypertension Clinical Trial

Official title:

A 4-Week, Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel Group Study To Evaluate The Safety, Tolerability And Efficacy Of Once Daily PF-04971729 And Hydrochlorothiazide In Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic And Blood Pressure Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01096667
• Other study ID #: 8835-042
• Secondary ID: B1521004MK-8835-
• Status: Completed
• Phase: Phase 2
• Start date: May 17, 2010
• Est. completion date: February 25, 2011

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: February 25, 2011
• Est. primary completion date: February 9, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension

Intervention

Drug:
• Placebo to Ertuglilflozin 1 or 5 mg
Placebo to ertuglilflozin tablet 1 or 5 mg once daily for 28 days
• Ertugliflozin 1 mg
Ertugliflozin tablet 1 mg once daily for 28 days
• Ertugliflozin 5 mg
Ertugliflozin tablet 5 mg once daily for 28 days
• Ertugliflozin 25 mg
Ertugliflozin tablet 25 mg once daily for 28 days
• HCTZ 12.5mg
Hydrocholorthiazide (HCTZ) 12.5 mg capsule once daily for 28 days
• Placebo to HCTZ
Placebo to HCTZ 12.5 mg capsule once daily for 28 days
• Placebo to ertuglilflozin 25 mg
Placebo to ertuglilflozin tablet 25 mg once daily for 28 days

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Pfizer

References & Publications (1)

Amin NB, Wang X, Mitchell JR, Lee DS, Nucci G, Rusnak JM. Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension. D — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline 24-hour Average Systolic Blood Pressure (SBP)	Baseline 24-hour average SBP was assessed using 24-hour ambulatory blood pressure monitoring (ABPM).	24 hours
Primary	Change From Baseline on 24-hour Average SBP at 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).	Baseline and Week 4
Secondary	Baseline Average 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.	Daytime: 16 hours; Nighttime: 8 hours
Secondary	Change From Baseline on Daytime Average SBP at 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.	Baseline and Week 4
Secondary	Change From Baseline on Nighttime Average SBP at 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 and Week 4
Secondary	Baseline 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.	Baseline
Secondary	Change From Baseline in Seated, Triplicate Trough SBP at 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 and Week 4
Secondary	Baseline 24-hour, Daytime and Nightime Average Diastolic Blood Pressure (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.	up to 24 hours
Secondary	Change From Baseline on 24-hour Average DBP at 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 and Week 4
Secondary	Change From Baseline on Daytime Average DBP at 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.	Baseline and Week 4
Secondary	Change From Baseline on Nighttime Average DBP at 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 and Week 4
Secondary	Baseline 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.	Baseline
Secondary	Change From Baseline in Seated, Triplicate Trough DBP at 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.	Baseline and Week 4
Secondary	Baseline 24-hour, Daytime and Nightime Average 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.	up to 24 hours
Secondary	Change From Baseline on 24-hour Average Heart Rate at Week 4	Change from baseline in 24-hour average heart rate at Week 4 using 24 hour ABPM.	Baseline and Week 4
Secondary	Change From Baseline on Daytime Average Heart Rate at 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.	Baseline and Week 4
Secondary	Change From Baseline on Nighttime Average Heart Rate at 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 and Week 4
Secondary	Baseline 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.	Baseline
Secondary	Change From Baseline in Seated, Triplicate Trough Heart Rate at 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 and Week 4
Secondary	Baseline 24-hour 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).	24 hours
Secondary	Change From Baseline on 24-hour Urinary Glucose Excretion at 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 and Week 4
Secondary	Baseline Fasting Plasma Glucose (FPG)	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).	Baseline
Secondary	Change From Baseline in FPG at Week 4	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).	Baseline and Week 4
Secondary	Change From Baseline in FPG at Week 2	For FPG, blood was drawn after an overnight fast of at least 8 hours (except water).	Baseline and Week 2
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	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.	Up to 63 days (including run-in, treatment period, and follow-up)
Secondary	Number of Participants Who Discontinued Study Drug Due to an AE	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.	Up to 28 days (treatment period)