Efficacy and Safety of Alogliptin 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 dose-response relationships of alogliptin, once daily (QD) to an α-glucosidase inhibitor, three times daily (TID), to determine the optimal clinical dose for type 2 diabetic patients.

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. To evaluate the long-term safety and efficacy of alogliptin, participants in the present study could enter a long-term extension study SYR-322/OCT-001 (NCT01263496) that was planned separately.

Official Title
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A Phase 2, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Determine the Efficacy and Safety of SYR-322 in Subjects With Type 2 Diabetes in Japan

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Voglibose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A glycosylated hemoglobin (HbA1c) value of 6.5% or more and below 10.0% 4 weeks after the start of screening(Week -4). A HbA1c differences within 10.0%* (*rounded off to the first decimal point) at the start of screening (Week -8) and 4 weeks after the start of screening (Week -4) from the HbA1c value at the start of screening. Was receiving a specific diet therapy and an exercise therapy (if any) for the last 4 weeks or longer before the start of screening (Week -8). Exclusion Criteria: Received any antidiabetic drug within the last 4 weeks before the start of screening (Week -8) or during screening.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo-matching tablets, orally, once or three times daily for up to 12 weeks.<br>|
| Experimental: Alogliptin 6.25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks<br>* Other names: SYR-322;|
| Experimental: Alogliptin 12.5 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR-322;|
| Experimental: Alogliptin 25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks.<br>* Other names: SYR-322;|
| Experimental: Alogliptin 50 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks<br>* Other names: SYR-322;|
| Active Comparator: Voglibose 0.2 mg TID<br> | Drug: Voglibose<br>* Voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.<br>* Other names: BASEN®;|

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 fasting plasma glucose 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 fasting plasma glucose 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 fasting plasma glucose 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 fasting plasma glucose collected at baseline. | Baseline and Week 12. | 
| Change From Baseline in Fasting C-peptide (Week 2). | The change between the value of fasting C-peptide collected at week 2 and fasting C-peptide collected at baseline. | Baseline and Week 2. | 
| Change From Baseline in Fasting C-peptide (Week 4). | The change between the value of fasting C-peptide collected at week 4 and fasting C-peptide collected at baseline. | Baseline and Week 4. | 
| Change From Baseline in Fasting C-peptide (Week 8). | The change between the value of fasting C-peptide collected at week 8 and fasting C-peptide collected at baseline. | Baseline and Week 8. | 
| Change From Baseline in Fasting C-peptide (Week 12). | The change between the value of fasting C-peptide collected at week 12 or final visit and fasting C-peptide collected at baseline. | Baseline and Week 12. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). | The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal. | Baseline and Week 12. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). | The change between the value of blood glucose collected at week 12 or final visit and blood glucose collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and at 2 hours after the start of the meal. | Baseline and Week 12. | 
| Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). | The change between the value of insulin collected at week 12 or final visit and insulin collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal. | Baseline and Week 12 | 
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). | The change between the value of C-peptide collected at week 12 or final visit and C-peptide collected at baseline as measured by the meal tolerance test. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon through blood samples drawn before a meal and 2 hours after the start of the meal. | Baseline and Week 12. | 
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). | The change between the value of glucagons collected at week 12 or final visit and glucagons collected at baseline. Meal tolerance test measures blood glucose, insulin, C-peptide and glucagon 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 - Type 2, Diabetes Mellitus, Drug Therapy