Dose-ranging Study to Evaluate the Effectiveness and Tolerability of MK0736 in Patients With Type 2 Diabetes Mellitus (T2DM) and Hypertension (0736-007)

A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy & Tolerability of MK0736 When Added to Ongoing Therapy With Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) in Patients With T2DM and Hypertension

The study will assess the efficacy and tolerability of MK0736 in patients with Type 2 Diabetes Mellitus and Hypertension who are on ongoing therapy with Angiotensin-Converting Enzyme or Angiotensin Receptor Blocker. After a 3 to 5 week pre-randomization phase, patients will be randomized to either MK0736 (3 doses), placebo, or hydrochlorothiazide (HCTZ). The study will also include a 3 week, posttreatment follow-up period.

Study Overview

• Status: Terminated
• Conditions: Hypertension; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Comparator: Placebo; Drug: MK-0736; Drug: Comparator: HCTZ

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be 18 to 75 years of age
• Type 2 Diabetes Mellitus (Glycohemoglobin [A1CHbA1c]: 7 to 10%)
• Hypertension: Diastolic blood pressure (DBP; 85 to 99 mm Hg) and systolic blood pressure (SBP; 120 to 159 mm Hg)
• LDL-C < 140 mg/dL
• On stable treatment with an Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB)

Exclusion Criteria:

• History of Type I Diabetes mellitus or ketoacidosis
• Patients taking 3 or more blood pressure lowering medications
• Have severe chronic heart failure
• History of certain diseases or conditions such as cardiac arrhythmias, heart attack, stroke, unstable angina, or decompensated vascular disease
• History of cancer within the last 5 years
• Human immunodeficiency virus (HIV) Positive
• Have received treatment with any investigational drugs within the past 30 days
• History of alcohol or drug abuse within the past 3 years
• Body Mass Index ( BMI) >= 41 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-0736 0.5 mg; One MK-0736 0.5 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will then be switched to MK-0736 8.0 mg, once daily for an additional 52 weeks (Phase B).	Drug: MK-0736
Experimental: MK-0736 2.0 mg; One MK-0736 2.0 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will then be switched to MK-0736 8.0 mg, once daily for 52 weeks (Phase B).	Drug: MK-0736
Experimental: MK-0736 8.0 mg; One MK-0736 8.0 mg tablet, orally, once daily for 24 weeks (Phase A). Participant will continue to receive MK-0736 8.0 mg, once daily for 52 weeks (Phase B).	Drug: MK-0736
Active Comparator: HCTZ 12.5 mg → MK-0736 8.0 mg; one 12.5 mg hydrochlorothiazide (HCTZ) tablet daily, orally, for 12 weeks. Participant then switched to MK-0736 8.0 mg for 12 weeks (Phase A). Participant will continue to receive MK-0736 8.0 mg, once daily for an additional 52 weeks (Phase B).	Drug: MK-0736; Drug: Comparator: HCTZ
Placebo Comparator: Placebo; One placebo tablet daily, orally, for 24 weeks (Phase A). Participant will continue to receive placebo, once daily for 52 weeks (Phase B)	Drug: Comparator: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sitting Diastolic Blood Pressure (SiDBP) at Week 12	Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average of the last 5 measurement was recorded.	Baseline and Week 12
Change From Baseline in Sitting Systolic Blood Pressure (SiSBP) at Week 12	Participant remained in the sitting position for at least 5 minutes before any blood pressure readings were recorded. Systolic and diastolic blood pressures were determined by taking 6 replicate measurements obtained 1 to 2 minutes apart. First reading was discarded and the average the last 5 measurement was recorded.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12	LDL-C calculated by the method of Friedewald equation at baseline and after 12 weeks of study drug administration	Baseline and Week 12
Change From Baseline in Body Weight at Week 24	Fasting weight was assessed at baseline and after 24 weeks of study drug administration and was measured after voiding, with shoes and socks off, wearing clinic gown to reduce variability and maintain consistency. Same standardized digital scale was used throughout the study.	Baseline and Week 24
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 24	HbA1c reported as a % and was measured at baseline and after 24 weeks of study drug administration	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: December 10, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Estimate): September 21, 2015
• Last Update Submitted That Met QC Criteria: September 18, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 0736-007; MK0736-007; 2008_600