Dose Range Finding Study of MK-0941 in Patients With Type 2 Diabetes Mellitus on Insulin (MK-0941-007 AM3 EXT1 AM1)(TERMINATED)

A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Range Finding Clinical Trial of MK0941 in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Insulin

The purpose of this study is to test the effect of MK-0941 as add-on therapy for participants taking insulin for type 2 diabetes mellitus. The primary hypotheses of this study are that treatment with MK-0941 added to insulin will provide greater reduction in hemoglobin A1c (HbA1c) level than will placebo added to insulin at 14 weeks, and that MK-0941 will be well-tolerated at 1 or more doses that demonstrate efficacy.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: MK-0941; Biological: Lantus; Drug: Metformin; Drug: Comparator: Placebo

Detailed Description

This study is a 54-week randomized, double-blind base study with an optional 104-week extension study (MK-0941-007-11). Beginning on Week 16, participants not randomized to the maximum dose of MK-0941 could up-titrate to MK-0941 40 mg three times daily. Participants who complete the 54-week base study are eligible to enter the extension study and will remain in the treatment group to which they were assigned in the base study.

• Study Type: Interventional
• Enrollment (Actual): 813
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• has type 2 diabetes mellitus
• has body mass index >20 and <43 kg/m^2
• is a male, or a female who is unlikely to conceive
• currently on a stable dose of insulin with or without metformin for Type 2 diabetes mellitus

Extension Study Inclusion Criteria:

• completed the base study either on double-blind study medication or as part of the post-treatment follow up population
• had ≥85% compliance with double-blind and open-label medication during the base study double-blind treatment period

Exclusion Criteria:

• has any history of Type 1 diabetes mellitus or ketoacidosis
• has received more that 1 week of thiazolidinedione (such as pioglitazone or rosiglitazone) therapy or injectable increatin-based therapy (such as Byetta) within the prior 8 weeks
• has had ≥2 episodes during their lifetime or >1 episode within the past year resulting in hypoglycemic seizures, comas, or unconsciousness
• is on a weight loss program and is not in the maintenance phase, or patient is taking a weight loss medication (e.g., orlistat, sibutramine, rimonabant) within 8 weeks of Visit 1
• has undergone surgery within 30 days prior to Visit 1 or has planned major surgery

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
Placebo Comparator: Placebo	Biological: Lantus; Lantus injection once daily; Other Names: Insulin glargine injection; Drug: Metformin; Metformin ≥1500 mg/day at a stable dose for at least 6 weeks before Screening and for the duration of the study. The number of randomized participants who receive metformin will be capped at 70% of enrollment.; Drug: Comparator: Placebo; Matching placebo to MK-0941 three times daily
Experimental: MK-0941 10 mg	Drug: MK-0941; MK-0941 tablets three times daily; Biological: Lantus; Lantus injection once daily; Other Names: Insulin glargine injection; Drug: Metformin; Metformin ≥1500 mg/day at a stable dose for at least 6 weeks before Screening and for the duration of the study. The number of randomized participants who receive metformin will be capped at 70% of enrollment.
Experimental: MK-0941 20 mg	Drug: MK-0941; MK-0941 tablets three times daily; Biological: Lantus; Lantus injection once daily; Other Names: Insulin glargine injection; Drug: Metformin; Metformin ≥1500 mg/day at a stable dose for at least 6 weeks before Screening and for the duration of the study. The number of randomized participants who receive metformin will be capped at 70% of enrollment.
Experimental: MK-0941 30 mg	Drug: MK-0941; MK-0941 tablets three times daily; Biological: Lantus; Lantus injection once daily; Other Names: Insulin glargine injection; Drug: Metformin; Metformin ≥1500 mg/day at a stable dose for at least 6 weeks before Screening and for the duration of the study. The number of randomized participants who receive metformin will be capped at 70% of enrollment.
Experimental: MK-0941 40 mg	Drug: MK-0941; MK-0941 tablets three times daily; Biological: Lantus; Lantus injection once daily; Other Names: Insulin glargine injection; Drug: Metformin; Metformin ≥1500 mg/day at a stable dose for at least 6 weeks before Screening and for the duration of the study. The number of randomized participants who receive metformin will be capped at 70% of enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin A1c (HbA1c) Level	Least square means change from baseline in HbA1c. HbA1c represents the percentage of glycated hemoglobin. A negative number means reduction in HbA1c level.	Baseline and Weeks 14, 54, 106, and 158
Percentage of Participants Who Experienced at Least One Adverse Event		Entire study including 54-week study and 104-week extension
Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event		Entire study including 54-week study and 104-week extension

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Two-hour Post Meal Glucose Level	Least squares mean change from baseline in 2-hour post meal glucose level.	Baseline and Weeks 14, 54, 106, and 158
Change in the Fasting Plasma Glucose Level	Least squares mean change from baseline in fasting plasma glucose.	Baseline and Weeks 14, 54, 106, and 158
Percentage of Participants Who Achieve an HbA1c of <7.0%		Weeks 106 and 158
Percentage of Participants Achieving an HbA1c of <7.0% at Week 54 Who Maintain an HbA1c of <7.0%		Weeks 54, 106 and 158

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Meininger GE, Scott R, Alba M, Shentu Y, Luo E, Amin H, Davies MJ, Kaufman KD, Goldstein BJ. Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes. Diabetes Care. 2011 Dec;34(12):2560-6. doi: 10.2337/dc11-1200. Epub 2011 Oct 12.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: October 3, 2008
• First Submitted That Met QC Criteria: October 3, 2008
• First Posted (Estimate): October 6, 2008

Study Record Updates

• Last Update Posted (Estimate): February 19, 2015
• Last Update Submitted That Met QC Criteria: February 2, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Insulin Glargine
• Other Study ID Numbers: 0941-007; 2008_557