MK0431 and Pioglitazone Co-Administration Factorial Study in Patients With Type 2 Diabetes Mellitus (0431-102 AM2)

Study Overview
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Brief Summary
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A study to evaluate the efficacy and safety of sitagliptin and pioglitazone co-administration in comparison with sitagliptin and pioglitazone monotherapy in patients with type 2 diabetes.

Official Title
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A Multicenter, Randomized, Double-Blind Study of the Co-Administration of Sitagliptin and Pioglitazone 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: Sitagliptin phosphate
* Drug: Pioglitazone hydrochloride
* Drug: Matching placebo to sitagliptin
* Drug: Matching placebo to pioglitazone
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is highly unlikely to conceive Patient meets one of the 3 categories is naïve to all antihyperglycemic agent (AHA) therapies, or is non-naïve based upon the patient's current diet, medical regimen and screening A1c patient is currently not on AHA with a screening A1c >=7.5 % and =<11.0 % patient is currently on either metformin pr sulfonylurea monotherapy with a screening A1c >=7.0 % and =<9.0 % Exclusion Criteria Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or has C=peptide value of =<0.8 ng/mL Patient has previously been treated with insulin, thiazolidinedione (TZD) (rosiglitazone or pioglitazone), any Dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin, vildagliptin, or alogliptin), exenatide or has previously been in a clinical study with any DPP-4 inhibitor or incretin mimetic Patient is on a weight loss program and is not in the maintenance phase or has started a weight loss medication (e.g. orlistat or sibutramine) within the prior 8 weeks Patient has undergone surgery within the prior 30 days or has major surgery planned during the study Patient has a medical history of active liver disease including chronic active hepatitis B or C or symptomatic gallbladder disease including primary biliary cirrhosis Patient has received treatment with an investigational product within 12 weeks prior to Visit 1

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin 100 mg<br> | Drug: Sitagliptin phosphate<br>* Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.<br>* Other names: Ristaben;Drug: Matching placebo to pioglitazone<br>* Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks.<br>Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Pioglitazone 15 mg<br> | Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Matching placebo to sitagliptin<br>* Matching placebo to sitagliptin orally once daily for 54 weeks.<br>Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Pioglitazone 30 mg<br> | Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Matching placebo to sitagliptin<br>* Matching placebo to sitagliptin orally once daily for 54 weeks.<br>Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Pioglitazone 45 mg<br> | Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Matching placebo to sitagliptin<br>* Matching placebo to sitagliptin orally once daily for 54 weeks.<br>Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Sitagliptin 100 mg/ Pioglitazone 15 mg<br> | Drug: Sitagliptin phosphate<br>* Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.<br>* Other names: Ristaben;Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Sitagliptin 100 mg/ Pioglitazone 30 mg<br> | Drug: Sitagliptin phosphate<br>* Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.<br>* Other names: Ristaben;Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|
| Experimental: Sitagliptin 100 mg/ Pioglitazone 45 mg<br> | Drug: Sitagliptin phosphate<br>* Sitagliptin 100 mg tablet (blinded) orally once daily for 54 weeks.<br>* Other names: Ristaben;Drug: Pioglitazone hydrochloride<br>* Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4.<br>* Other names: Actos;Drug: Metformin<br>* Metformin 500 mg (open-label) was to be initiated as rescue therapy to participants not meeting specific glycemic goals. The dose of metformin may have been uptitrated and adjusted, at the discretion of the investigator, up to the maximum approved dose in the country of origin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1C (A1C) at Week 24 | A1C represents the percentage of glycosylated hemoglobin. | Baseline and Week 24 | 
| Change From Baseline in A1C at Week 54 | A1C represents the percentage of glycosylated hemoglobin. | Baseline and Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |  | Baseline and Week 24 | 
| Change From Baseline in 2-Hour Post-meal Glucose (PMG) at Week 24 | PMG was measured using the Meal Tolerance Test (MTT). | Baseline and Week 24 | 
| Change From Baseline in FPG at Week 54 |  | Baseline and Week 54 | 
| Change From Baseline in 2-Hour PMG at Week 54 | PMG was measured using the Meal Tolerance Test (MTT). | Baseline and Week 54 |