Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136)

Study Overview
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Brief Summary
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This study will evaluate the effect of the addition of metformin once daily (q.d.) or twice daily (b.i.d.) to sitagliptin monotherapy in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control with diet/exercise therapy and sitagliptin monotherapy. The primary hypotheses are that the addition of metformin 250 mg b.i.d. or metformin 500 mg q.d. is superior to the addition of placebo on the change from baseline in hemoglobin A1c (HbA1c) at 24 weeks and that the addition of metformin 500 mg q.d. is non-inferior to the addition of metformin 250 mg b.i.d. on the change from baseline in HbA1c at 24 weeks.

Official Title
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A Phase III, Randomized, Placebo and Active-Controlled, Double-Blind Clinical Trial to Study the Efficacy and Safety of the Addition of Metformin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet/Exercise Therapy and Sitagliptin Monotherapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Metformin
* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Mellitus (T2DM) Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 4 weeks, on any additional oral hypoglycemic agent (AHA) in the prior 8 weeks, and HbA1c ≥ 6.0% and ≤ 9.0%; or Currently being treated with diet/exercise and on stable dose of sitagliptin for ≥ 10 weeks, not on any additional oral AHA in the prior 8 weeks, and HbA1c ≥ 6.5% and < 10.0% Exclusion Criteria: Type 1 diabetes mellitus, Secondary diabetes mellitus, or Gestational diabetes mellitus

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 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: Metformin 500 mg q.d.<br>Participants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. | Drug: Sitagliptin<br>* Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)<br>* Other names: MK-0431/ONO-5435;Drug: Metformin<br>* Metformin, orally, 500 mg daily (single dose; two 250 mg tablets) for 24 weeks<br>Drug: Placebo<br>* Placebo to match metformin 250 mg tablets, orally, for 24 weeks<br>|
| Experimental: Metformin 250 mg b.i.d.<br>Participants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. | Drug: Sitagliptin<br>* Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)<br>* Other names: MK-0431/ONO-5435;Drug: Metformin<br>* Metformin, orally, 500 mg daily (divided dose; 250 mg tablet b.i.d.) for 24 weeks<br>Drug: Placebo<br>* Placebo to match metformin 250 mg tablets, orally, for 24 weeks<br>|
| Placebo Comparator: Placebo<br>Participants will receive sitagliptin daily (continuing their pre-study dose), 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. | Drug: Sitagliptin<br>* Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose)<br>* Other names: MK-0431/ONO-5435;Drug: Placebo<br>* Placebo to match metformin 250 mg tablets, orally, for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) | Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. | Baseline and Week 24 | 
| Percentage of Participants Who Experienced at Least One Adverse Event |  | Up to 26 weeks | 
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event |  | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. | Baseline and Week 24 |