MK0431 (Sitagliptin) and Metformin Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-036)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of an investigational drug in patients with Type 2 Diabetes Mellitus (T2DM) (a specific type of diabetes).

Official Title
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A Multicenter, Randomized, Double-Blind Factorial Study of the Co-Administration of MK0431 and Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)
* Drug: Comparator: MK0431 100 mg q.d. (q.d. = once daily)
* Drug: Comparator: Placebo (Phase A)/Metformin (Phase B)
* Drug: Comparator: Metformin 500 mg b.i.d.
* Drug: Comparator: Open-Label MK0431/Metformin 50/1000 mg b.i.d.
* Drug: Comparator: Metformin 1000 mg b.i.d.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 54-Week Base Study: Patients between the ages of 18 and 78 with Type 2 Diabetes Mellitus (a specific type of diabetes) 50-Week Extension Study: Patients who complete the 54-week base study are eligible to enter the 50-week extension study Exclusion Criteria: Patients who do not have Type 2 Diabetes Mellitus (a specific type of diabetes)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MK0431 100 mg q.d. | Drug: Comparator: MK0431 100 mg q.d. (q.d. = once daily)<br>* MK0431 oral tablets will be started on Day 1 as two 50 mg tablets (100 mg q.d.) (q.d. = once daily) and continued at this dose throughout the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>|
| Active Comparator: 2<br>Metformin 500 mg b.i.d. | Drug: Comparator: Metformin 500 mg b.i.d.<br>* Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>|
| Active Comparator: 3<br>Metformin 1000 mg b.i.d. | Drug: Comparator: Metformin 1000 mg b.i.d.<br>* Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>|
| Experimental: 4<br>Coadministration of MK0431 and Metformin 50/500 mg b.i.d. | Drug: Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)<br>* MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>* Other names: MK0431;Drug: Comparator: Metformin 500 mg b.i.d.<br>* Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased after 1 week to a stable dose of 500 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 500 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>|
| Experimental: 5<br>Coadministration of MK0431 and Metformin 50/1000 mg b.i.d. | Drug: Comparator: MK0431 50 mg b.i.d. (b.i.d. = twice daily)<br>* MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take MK0431 50 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>* Other names: MK0431;Drug: Comparator: Metformin 1000 mg b.i.d.<br>* Metformin oral tablets will be started on Day 1 at 500 mg q.d. (q.d. = once daily) and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. (b.i.d. = twice daily) Patients will continue to take metformin 1000 mg b.i.d. for the remainder of the 54-week base study (including the 24-week placebo-controlled Phase A and 30-week active-controlled Phase B) and during the 50-week extension study (for patients who complete the 54-week base study and enter the 50-week extension study) for a total treatment duration of up to 104 weeks.<br>|
| Placebo Comparator: 6<br>Placebo/Metformin 1000 mg b.i.d. | Drug: Comparator: Placebo (Phase A)/Metformin (Phase B)<br>* During the placebo-controlled period (Day 1 through Week 24/Phase A), metformin and MK0431 matching placebos will be dispensed as oral tablets. At the beginning of the 30-week active-controlled period (Phase B), metformin will be started as 500 mg q.d. (q.d. = once daily) and up-titrated in 500 mg weekly increments to a stable dose of 1000 mg b.i.d. Patients who complete the 54-week base study and who enter the 50-week extension study will continue to take metformin 1000 mg b.i.d. (b.i.d. = twice daily) for a total placebo/metformin treatment duration of up to 104 weeks.<br>|
| Experimental: 7<br>Non-Randomized, Open-Label: Coadministration MK0431 and Metformin 50/1000 mg b.i.d. | Drug: Comparator: Open-Label MK0431/Metformin 50/1000 mg b.i.d.<br>* MK0431 oral tablets will be started on Day 1 at 50 mg q.d. (q.d. = once daily) and increased after one week to a stable dose of 50 mg b.i.d. (b.i.d. = twice daily) Metformin oral tablets will be started on Day 1 at 500 mg q.d. and increased by increments of 500 mg per week to achieve a stable dose of 1000 mg b.i.d. The open-label treatment period is 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24 | HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. | Week 24 | 
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. | Week 24 | 
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | HbA1c is measured as a percent. This change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. | Week 54 | 
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. | Week 54 | 
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. | Week 54 | 
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104 | HbA1c is measured as a percent. This change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent. | Week 104 | 
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104 | Change from baseline at Week 104 is defined as Week 104 minus Week 0. | Week 104 | 
| Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104 | Change from baseline at Week 104 is defined as Week 104 minus Week 0. | Week 104 |