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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus, Hypertension

Intervention / Treatment
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* Drug: MK-0736
* Drug: Comparator: Placebo
* Drug: Comparator: HCTZ


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0736 0.5 mg<br>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<br> <br> |
| Experimental: MK-0736 2.0 mg<br>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<br> <br> |
| Experimental: MK-0736 8.0 mg<br>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<br> <br> |
| Active Comparator: HCTZ 12.5 mg → MK-0736 8.0 mg<br>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<br> <br> Drug: Comparator: HCTZ<br> <br> |
| Placebo Comparator: Placebo<br>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<br> <br> |

What is the study measuring?
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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 |