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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: MK-0941
* Drug: Comparator: Placebo
* Biological: Lantus
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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-0941 10 mg<br> | Drug: MK-0941<br>* MK-0941 tablets three times daily<br>Biological: Lantus<br>* Lantus injection once daily<br>* Other names: Insulin glargine injection;Drug: Metformin<br>* 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.<br>|
| Experimental: MK-0941 20 mg<br> | Drug: MK-0941<br>* MK-0941 tablets three times daily<br>Biological: Lantus<br>* Lantus injection once daily<br>* Other names: Insulin glargine injection;Drug: Metformin<br>* 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.<br>|
| Experimental: MK-0941 30 mg<br> | Drug: MK-0941<br>* MK-0941 tablets three times daily<br>Biological: Lantus<br>* Lantus injection once daily<br>* Other names: Insulin glargine injection;Drug: Metformin<br>* 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.<br>|
| Experimental: MK-0941 40 mg<br> | Drug: MK-0941<br>* MK-0941 tablets three times daily<br>Biological: Lantus<br>* Lantus injection once daily<br>* Other names: Insulin glargine injection;Drug: Metformin<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Drug: Comparator: Placebo<br>* Matching placebo to MK-0941 three times daily<br>Biological: Lantus<br>* Lantus injection once daily<br>* Other names: Insulin glargine injection;Drug: Metformin<br>* 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.<br>|

What is the study measuring?
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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 |