Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105)

Study Overview
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Brief Summary
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This study is being done to evaluate the safety, efficacy, and dose level of sitagliptin (MK-0431/ONO-5435) used once daily (qd) in Japanese participants with impaired glucose tolerance who have inadequate glycemic control using diet and exercise therapy.

Official Title
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A Phase II, Randomized, Placebo-Controlled, Parallel-group, Double-Blind, Dose Response Finding Clinical Trial to Study the Efficacy and Safety of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance Who Have Inadequate Glycemic Control on Diet/Exercise Therapy

Conditions
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Glucose Intolerance

Intervention / Treatment
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* Drug: Placebo for Sitagliptin 25 mg
* Drug: Placebo for Sitagliptin 50 mg
* Drug: Sitagliptin 25 mg
* Drug: Sitagliptin 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Impaired glucose tolerance On diet/exercise therapy Unlikely to conceive Meets all of the following glycemic parameters: Hemoglobin A1c (Japan Diabetes Society value) <6.1%, Fasting Plasma Glucose <126 mg/dL, and 2-hr plasma glucose level in 75g oral glucose tolerance test ≥140 mg/dL and <200 mg/dL Exclusion Criteria: History of diabetes mellitus Disease or condition of clear or likely glucose tolerance disorder Previously treated with a drug to prevent diabetes and/or any antihyperglycemic drug

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will take one tablet of placebo for sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks. | Drug: Placebo for Sitagliptin 25 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>Drug: Placebo for Sitagliptin 50 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>|
| Experimental: Sitagliptin 25 mg<br>Participants will take one tablet of sitagliptin 25 mg and one tablet of placebo for sitagliptin 50 mg orally once daily for 8 weeks. | Drug: Placebo for Sitagliptin 50 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>Drug: Sitagliptin 25 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>* Other names: MK-0431/ONO-5435;|
| Experimental: Sitagliptin 50 mg<br>Participants will take one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks. | Drug: Placebo for Sitagliptin 25 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>Drug: Sitagliptin 50 mg<br>* 1 tablet orally once daily before breakfast for 8 weeks<br>* Other names: MK-0431/ONO-5435;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for Meal Tolerance Test (MTT) at Week 8 | Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal. | Baseline (Week 0) and Week 8 | 
| Percentage of Participants Who Experienced One or More Adverse Events (AEs) | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. | Up to 10 weeks | 
| Percentage of Participants Who Discontinued Treatment Due to an Adverse Event (AE) | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Glucose Total Area Under the Concentration Curve 0 to 2 Hours (AUC 0-2 Hrs) for 75-gram Oral Glucose Tolerance Test (OGTT) at Week 7 | Glucose total AUC 0-2 hours for 75 g OGTT was measured at Baseline (Week -1) and at Week 7. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at 75 g glucose loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 7, participants received study drug or placebo 30 minutes prior to loading 75 g glucose solution. | Baseline (Week -1) and Week 7 |