Efficacy and Safety of Alogliptin Used Combination With Thiazolidine in Participants With Type 2 Diabetes in Japan

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy and safety of alogliptin, once daily (QD) combined with a thiazolidine taken QD in type 2 diabetic patients with uncontrolled blood glucose.

Detailed Description
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Both insulin hyposecretion and insulin-resistance are considered to be involved in the development of type 2 diabetes mellitus. Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV (DPP-IV) enzyme. DPP-IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of DPP-IV will improve glycemic control in patients with type 2 diabetes. The present study was planned to evaluate the efficacy and safety of alogliptin as an add-on to pioglitazone in type 2 diabetic patients with uncontrolled blood glucose despite treatment with pioglitazone as well as diet and exercise therapies.

Official Title
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A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of SYR-322 When Used in Combination With Thiazolidine in Subjects With Type 2 Diabetes in Japan

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Alogliptin and pioglitazone
* Drug: Alogliptin and pioglitazone
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had been taking pioglitazone at a stable dose (15 mg/day or 30 mg/day) for at least 16 weeks prior to the start of the treatment period (Week 0). Had glycosylated hemoglobin (HbA1c) of 6.5% or more and below 10.0% at 14 weeks after the start of the observation period (Week -2). Had HbA1c difference within 10.0%* at 10 weeks after the start of the observation period (Week -6) and 14 weeks after the start of the observation period (Week -2) from 10 weeks after the start of the observation period (Week -6) (*rounded off to the first decimal place). Was receiving specific diet and exercise (if any) therapies during the observation period. Exclusion Criteria: Had taken a diabetic medications other than pioglitazone within 16 weeks before the start of the treatment period (Week 0). Had a history or symptoms of cardiac failure.

Ages Eligible for Study
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Minimum Age: 33 Years
Maximum Age: 88 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alogliptin 12.5 mg QD and Pioglitazone 15 or 30mg QD<br> | Drug: Alogliptin and pioglitazone<br>* Alogliptin 12.5mg, tablets, orally, once daily and Pioglitazone 15 or 30 mg, tablets orally once daily for up 12 weeks.<br>* Other names: Pioglitazone: Actos®;|
| Experimental: Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD<br> | Drug: Alogliptin and pioglitazone<br>* Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 or 30 mg, tablets orally once daily for up 12 weeks.<br>* Other names: Pioglitazone: Actos®;|
| Active Comparator: Pioglitazone (15mg or 30mg ) QD<br> | Drug: Pioglitazone<br>* Pioglitazone 15 or 30 mg, tablets orally once daily for up 12 weeks.<br>* Other names: Pioglitazone: Actos®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (Week 12). | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 and glycosylated hemoglobin collected at baseline. | Baseline and Week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (Week 2). | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 2 and glycosylated hemoglobin collected at baseline. | Baseline and Week 2. | 
| Change From Baseline in Glycosylated Hemoglobin (Week 4). | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 4 and glycosylated hemoglobin collected at baseline. | Baseline and Week 4. | 
| Change From Baseline in Glycosylated Hemoglobin (Week 8). | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 8 and glycosylated hemoglobin collected at baseline. | Baseline and Week 8. | 
| Change From Baseline in Fasting Plasma Glucose (Week 2). | The change between the value of fasting plasma glucose collected at week 2 and glycosylated hemoglobin collected at baseline. | Baseline and Week 2. | 
| Change From Baseline in Fasting Plasma Glucose (Week 4). | The change between the value of fasting plasma glucose collected at week 4 and glycosylated hemoglobin collected at baseline. | Baseline and Week 4. | 
| Change From Baseline in Fasting Plasma Glucose (Week 8). | The change between the value of fasting plasma glucose collected at week 8 and glycosylated hemoglobin collected at baseline. | Baseline and Week 8. | 
| Change From Baseline in Fasting Plasma Glucose (Week 12). | The change between the value of fasting plasma glucose collected at week 12 or final visit and glycosylated hemoglobin collected at baseline. | Baseline and Week 12. | 
| Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12). | The change between the value of blood glucose measured by the meal tolerance test collected at week 12 or final visit and blood glucose measured by the meal tolerance test collected at baseline. Meal tolerance test measures blood glucose through blood samples drawn before a meal and 2 hours after the start of the meal. | Baseline and Week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus - Type2, Diabetes Mellitus, Drug Therapy