Efficacy and Safety of Alogliptin Used Combination With Metformin 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 evaluate the efficacy and safety of alogliptin, once dairy (QD) combined with metformin taken twice daily (BID) or three times daily (TID) 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 metformin in type 2 diabetic patients who have uncontrolled blood glucose despite treatment with metformin 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 Metformin 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 metformin
* Drug: Alogliptin and metformin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had been taking metformin at a stable dose regimen (500 mg/day twice daily after meal or 750 mg/day three times daily after meal) for at least 12 weeks prior to the initiation of the treatment period (Week 0). Had an glycosylated hemoglobin (HbA1c) of 6.5% or more and below 10.0% at 8 weeks after the initiation of the observation period (Week -4). Had an HbA1c difference between 4 weeks after the initiation of the observation period (Week -8) and 8 weeks after the initiation of the observation period (Week -4) being within 10.0%* of the value at 4 weeks after the initiation of the observation period (Week -8) (*rounded off to the first decimal place). Was receiving specific diet and exercise (if any) therapies during the observation period. Exclusion Criteria: Had taken other diabetic medications than metformin within 12 weeks before the initiation of the treatment period (Week 0). With a history or symptoms of lactic acidosis.

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 64 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 |
| --- | --- |
| Active Comparator: Alogliptin 12.5 mg QD and metformin 500mg BID or 750mg TID<br> | Drug: Alogliptin and metformin<br>* Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.<br>* Other names: Glycoran;|
| Active Comparator: Alogliptin 25mg QD and metformin 500mg BID or 750mg TID<br> | Drug: Alogliptin and metformin<br>* Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.<br>* Other names: Glycoran;|
| Active Comparator: Metformin 500mg BID or 750mg TID<br> | Drug: Metformin<br>* Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks.<br>* Other names: Glycoran;|

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 or final visit 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 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 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 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 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 at 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 - Type 2, Diabetes Mellitus, Drug Therapy