A Study of Different Doses of Sitagliptin (MK-0431) in Participants With Type 2 Diabetes Mellitus (MK-0431-014)

Study Overview
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Brief Summary
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A study of different doses of MK-0431 in participants with type 2 diabetes mellitus. There have been 3 extensions to the base study (Extension 1: up to Week 52, Extension 2: up to Week 106, and Extension 3: up to Week 158). The primary hypothesis for the study is that In participants with type 2 diabetes who have inadequate glycemic control, after 12 weeks of treatment, a dose-response will be seen across once-daily doses of MK-0431 in lowering hemoglobin A1C (HbA1c).

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose-Ranging Finding Study of Once-Daily Dosing of Sitaglipin (MK-0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Conditions
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Type II Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo to sitagliptin
* Drug: Metformin
* Drug: Rescue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and non-pregnant women Fasting plasma glucose >= 130 mg/dL HbA1c >=6.5% and >10.0% Exclusion Criteria: You have a history of type I diabetes You are on a weight loss program with ongoing weight loss or taking weight loss medication You have had surgery within 30 days You hvae hepatitis B or C.

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: Sitagliptin 25 mg once daily<br>Sitaglipin (MK-0431), 25 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. | Drug: Sitagliptin<br> <br> Drug: Rescue<br>* Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.<br>|
| Experimental: Sitagliptin 50 mg once daily<br>Sitagliptin, 50 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. | Drug: Sitagliptin<br> <br> Drug: Rescue<br>* Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.<br>|
| Experimental: Sitaglipin 100 mg once daily<br>Sitagliptin, 100 mg, once daily for 158 weeks, orally | Drug: Sitagliptin<br> <br> Drug: Rescue<br>* Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.<br>|
| Experimental: Sitagliptin 50 mg twice daily<br>Sitagliptin 50 mg, twice daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. | Drug: Sitagliptin<br> <br> Drug: Rescue<br>* Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.<br>|
| Placebo Comparator: Placebo to Sitagliptin → Metformin<br>Placebo to Sitagliptin, once daily, orally for 12 weeks. Participants randomized to the placebo treatment group during the base study were reallocated to treatment with metformin 850 mg twice daily (b.i.d., initiated with 850 mg q.d. for 4 weeks then force titrated to 850 mg b.i.d.) during either the first or initiation of the second extensions study periods. | Drug: Placebo to sitagliptin<br> <br> Drug: Metformin<br> <br> Drug: Rescue<br>* Patients whose FPG >240 mg/dL from Week 16 or HbA1C >8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently >240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C >8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C >7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1C at Week 12 |  | Baseline and Week 12 | 
| Number of Participants Who Experienced One or More Adverse Events (AE) up to Week 14 |  | Up to Week 14 | 
| Number of Participants Who Experienced One or More AE up to Week 54 |  | Up to Week 54 | 
| Number of Participants Who Experienced One or More AE up to Week 108 |  | Up to Week 108 | 
| Number of Participants Who Experienced One or More AE up to Week 160 |  | Up to Week 160 | 
| Number of participants Who Discontinued Study Treatment Due to An AE up to Week 12 |  | Up to Week 12 | 
| Number of participants Who Discontinued Study Treatment Due to An AE up to Week 52 |  | Up to Week 52 | 
| Number of participants Who Discontinued Study Treatment Due to An AE up to Week 106 |  | Up to Week 106 | 
| Number of participants Who Discontinued Study Treatment Due to An AE up to Week 158 |  | Up to Week 158 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in HbA1C at Week 52 |  | Baseline and Week 52 | 
| Change from Baseline in HbA1C at Week 106 |  | Baseline and Week 106 | 
| Change from Baseline in HbA1C at Week 158 |  | Baseline and Week 158 | 
| Change from Baseline in Fasting Plasma Glucose (FPG) at Week 12 |  | Baseline and Week 12 | 
| Change from Baseline in FPG at Week 52 |  | Baseline and Week 52 | 
| Change from Baseline in FPG at Week 106 |  | Baseline and Week 106 | 
| Change from Baseline in FPG at Week 158 |  | Baseline and Week 158 | 
| Change from Baseline in Body Weight at Week 12 |  | Baseline and Week 12 | 
| Change from Baseline in Body Weight at Week 52 |  | Baseline and Week 52 | 
| Change from Baseline in Body Weight at Week 106 |  | Baseline and Week 106 | 
| Change from Baseline in Body Weight at Week 158 |  | Baseline and Week 158 | 
| Change From Baseline in Serum Fructosamine at Week 12 |  | Baseline and Week 12 | 
| Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 12 |  | Baseline and Week 12 | 
| Change From Baseline in Daily Seven-Point Fingerstick Glucose Average at Week 52 |  | Baseline and Week 52 |