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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Alogliptin and metformin; Drug: Alogliptin and metformin; Drug: Metformin

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 metformin in type 2 diabetic patients who have uncontrolled blood glucose despite treatment with metformin as well as diet and exercise therapies.

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. 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).
3. 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).
4. Was receiving specific diet and exercise (if any) therapies during the observation period.

Exclusion Criteria:

1. Had taken other diabetic medications than metformin within 12 weeks before the initiation of the treatment period (Week 0).
2. With a history or symptoms of lactic acidosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Alogliptin 12.5 mg QD and metformin 500mg BID or 750mg TID	Drug: Alogliptin and metformin; Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.; Other Names: SYR-32; Glycoran; Drug: Alogliptin and metformin; Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.; Other Names: SYR-322; Glycoran
Active Comparator: Alogliptin 25mg QD and metformin 500mg BID or 750mg TID	Drug: Alogliptin and metformin; Alogliptin 12.5 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.; Other Names: SYR-32; Glycoran; Drug: Alogliptin and metformin; Alogliptin 25 mg, tablets, orally, once daily and metformin 250 mg, tablets, orally, twice or three times daily for up 12 weeks.; Other Names: SYR-322; Glycoran
Active Comparator: Metformin 500mg BID or 750mg TID	Drug: Metformin; Metformin 250 mg, tablets, orally, twice or three times daily and alogliptin placebo-matching tablets, orally, once daily for up 12 weeks.; Other Names: Glycoran

What is the study measuring?

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 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 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 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.

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Professor, Diabetes and Endocrine Division, Department of Medicine, Kawasaki Medical School

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: March 16, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (Estimate): March 18, 2011

Study Record Updates

• Last Update Posted (Estimate): February 3, 2012
• Last Update Submitted That Met QC Criteria: February 1, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Drug Therapy; Diabetes Mellitus; Diabetes Mellitus - Type 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Alogliptin
• Other Study ID Numbers: SYR-322/CCT-006; JapicCTI-080629 (Registry Identifier: JapicCTI); UMIN000001394 (Registry Identifier: UMIN-CTR); U1111-1119-6303 (Registry Identifier: WHO)