Efficacy and Safety of Alogliptin Used in Combination With α-glucosidase Inhibitor 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 an α-glucosidase inhibitor taken 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. In Japan, α-glucosidase inhibitors are widely used as a first-line treatment for type 2 diabetes mellitus. Because alogliptin has a different mechanism of action compared to α-glucosidase inhibitors, the study evaluated the efficacy and safety of alogliptin combined with an α-glucosidase inhibitor in type 2 diabetic patients with uncontrolled blood glucose while taking a α-glucosidase inhibitor and receiving diet and/or exercise therapies. To evaluate the long-term safety and efficacy of the concomitant use of alogliptin and an α-glucosidase inhibitor, subjects who participated in the present study could enter a long-term extension study SYR-322/OCT-003 (NCT01263509) that was planned separately.

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 α-glucosidase Inhibitor 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 voglibose
* Drug: Alogliptin and voglibose
* Drug: Voglibose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had been receiving a stable dose and regimen of an α-glucosidase inhibitor for the last 4 weeks or longer before the start of the screening phase (Week -8) and during the screening phase. Had a glycosylated hemoglobin (HbA1c) value of 6.5% or more and below 10.0% 4 weeks after the start of the screening phase (Week -4). Had HbA1c differences within 10.0% at the start of the screening phase (Week -8) and 4 weeks after the start of the screening phase (Week -4) from the HbA1c value at the start of the screening phase. Was receiving a specific diet therapy and an exercise therapy (if any) for the last 4 weeks or longer before the start of the screening phase (Week -8). Exclusion Criteria: Had received any antidiabetic drug other than α-glucosidase inhibitors within the last 4 weeks before the start of the screening phase (Week -8) or during the screening phase.

Ages Eligible for Study
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Minimum Age: 33 Years
Maximum Age: 85 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: Voglibose 0.2 mg TID<br> | Drug: Voglibose<br>* Alogliptin placebo-matching tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.<br>* Other names: BASEN®;|
| Experimental: Alogliptin 12.5 mg QD and Voglibose 0.2 mg TID<br> | Drug: Alogliptin and voglibose<br>* Alogliptin 12.5 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.<br>* Other names: Voglibose;|
| Experimental: Alogliptin 25 mg QD and Voglibose 0.2 mg TID<br> | Drug: Alogliptin and voglibose<br>* Alogliptin 25 mg, tablets, orally, once daily and voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.<br>* Other names: Voglibose;|

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 (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 (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 at 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 at 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 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