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

Phase 2

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Alogliptin and glimepiride; Drug: Glimepiride

• Registration Number: NCT01318083
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study was evaluate the efficacy and safety of alogliptin, once daily (QD) combined with an Sulfonylurea taken QD or twice daily (BID) in type 2 diabetic patients with uncontrolled blood glucose.

Detailed Description

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 sulfonylurea in type 2 diabetic patients who had uncontrolled blood glucose despite treatment with an sulfonylurea as well as diet and exercise therapies.

Study Timeline

• Study Start: 2008-08
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Study First Submitted: 2011-03-16
• Study First Submitted QC: 2011-03-17
• Study First Posted: 2011-03-18
• Results First Submitted: 2011-06-08
• Results First Submitted QC: 2011-06-08
• Results First Posted: 2011-07-06
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-01
• Last Update Posted: 2012-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 312

Inclusion Criteria

1. Had been taking a sulfonylurea for at least 4 weeks prior to the initiation of the observation period (Week -12).
2. Had been taking glimepiride at a stable dose regimen (1, 2, 3 or 4 mg/day, once or twice daily in the morning or in the morning and evening, before or after meal) for at least 12 weeks prior to the initiation of the treatment period (Week 0).
3. Had glycosylated hemoglobin (HbA1c) of 7.0% or more and below 10.0% at 8 weeks after the initiation of the observation period (Week -4).
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).
5. Was receiving specific diet and exercise (if any) therapies during the observation period.

Exclusion Criteria

1. Had taken other diabetic medications than glimepiride within 12 weeks before the initiation of the treatment period (Week 0).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alogliptin 25 mg QD and Glimepiride QD or BID	Alogliptin and glimepiride	-
Alogliptin 12.5 mg QD and Glimepiride QD or BID	Alogliptin and glimepiride	-
Glimepiride 1, 2, 3 or 4 mg QD or BID	Glimepiride	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Glycosylated Hemoglobin (Week 12).	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Fasting Plasma Glucose (Week 12).	Baseline and Week 12.	The change between the value of fasting plasma glucose collected at week 12 or final visit and baseline.
Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12).	Baseline and 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.
Change From Baseline in Glycosylated Hemoglobin (Week 2).	Baseline and 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.
Change From Baseline in Glycosylated Hemoglobin (Week 4).	Baseline and 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.
Change From Baseline in Glycosylated Hemoglobin (Week 8).	Baseline and 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.
Change From Baseline in Fasting Plasma Glucose (Week 2).	Baseline and Week 2.	The change between the value of fasting plasma glucose collected at week 2 and baseline.
Change From Baseline in Fasting Plasma Glucose (Week 4).	Baseline and Week 4.	The change between the value of fasting plasma glucose collected at week 4 and baseline.
Change From Baseline in Fasting Plasma Glucose (Week 8).	Baseline and Week 8.	The change between the value of fasting plasma glucose collected at week 8 and baseline.