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

• ClinicalTrials.gov Identifier: NCT01263470
• Recruitment Status: Completed
• First Posted: December 20, 2010
• Results First Posted: July 6, 2011
• Last Update Posted: February 3, 2012
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: Alogliptin; Drug: Voglibose; Drug: Placebo	Phase 2

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2007
• Actual Primary Completion Date: December 2007
• Actual Study Completion Date: December 2007

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo-matching tablets, orally, once or three times daily for up to 12 weeks.
Experimental: Alogliptin 6.25 mg QD	Drug: Alogliptin; Alogliptin 6.25 mg, tablets, orally, once daily for up to 12 weeks; Other Name: SYR-322
Experimental: Alogliptin 12.5 mg QD	Drug: Alogliptin; Alogliptin 12.5 mg, tablets, orally, once daily for up to 12 weeks.; Other Name: SYR-322
Experimental: Alogliptin 25 mg QD	Drug: Alogliptin; Alogliptin 25 mg, tablets, orally, once daily for up to 12 weeks.; Other Name: SYR-322
Experimental: Alogliptin 50 mg QD	Drug: Alogliptin; Alogliptin 50 mg, tablets, orally, once daily for up to 12 weeks; Other Name: SYR-322
Active Comparator: Voglibose 0.2 mg TID	Drug: Voglibose; Voglibose 0.2 mg, tablets, orally, three times daily for up to 12 weeks.; Other Names: Voglib; BASEN®

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Glycosylated Hemoglobin (Week 12). [ Time Frame: 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 :

1. Change From Baseline in Glycosylated Hemoglobin (Week 2). [ Time Frame: 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.
2. Change From Baseline in Glycosylated Hemoglobin (Week 4). [ Time Frame: 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.
3. Change From Baseline in Glycosylated Hemoglobin (Week 8). [ Time Frame: 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.
4. Change From Baseline in Fasting Plasma Glucose (Week 2). [ Time Frame: Baseline and Week 2 ]
   The change between the value of fasting plasma glucose collected at week 2 and fasting plasma glucose collected at baseline.
5. Change From Baseline in Fasting Plasma Glucose (Week 4). [ Time Frame: Baseline and Week 4. ]
   The change between the value of fasting plasma glucose collected at week 4 and fasting plasma glucose collected at baseline.
6. Change From Baseline in Fasting Plasma Glucose (Week 8). [ Time Frame: Baseline and Week 8. ]
   The change between the value of fasting plasma glucose collected at week 8 and fasting plasma glucose collected at baseline.
7. Change From Baseline in Fasting Plasma Glucose (Week 12). [ Time Frame: Baseline and 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.
8. Change From Baseline in Fasting C-peptide (Week 2). [ Time Frame: Baseline and Week 2. ]
   The change between the value of fasting C-peptide collected at week 2 and fasting C-peptide collected at baseline.
9. Change From Baseline in Fasting C-peptide (Week 4). [ Time Frame: Baseline and Week 4. ]
   The change between the value of fasting C-peptide collected at week 4 and fasting C-peptide collected at baseline.
10. Change From Baseline in Fasting C-peptide (Week 8). [ Time Frame: Baseline and Week 8. ]
    The change between the value of fasting C-peptide collected at week 8 and fasting C-peptide collected at baseline.
11. Change From Baseline in Fasting C-peptide (Week 12). [ Time Frame: Baseline and 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.
12. Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value). [ Time Frame: Baseline and Week 12. ]
    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.
13. Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC (0-2)). [ Time Frame: Baseline and Week 12. ]
    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.
14. Change From Baseline in Insulin Measured by Meal Tolerance Testing - Area Under the Curve at 2 Hours (AUC(0-2)). [ Time Frame: Baseline and Week 12 ]
    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.
15. Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2). [ Time Frame: Baseline and Week 12. ]
    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.
16. Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)). [ Time Frame: Baseline and Week 12 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Japan

Okayama, Japan, 701-0192

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Professor, Department of Medicine; Kawasaki Medical School

More Information

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01263470
• Other Study ID Numbers: SYR-322/CCT-001; U1111-1118-3752 ( Registry Identifier: WHO )
• First Posted: December 20, 2010
• Results First Posted: July 6, 2011
• Last Update Posted: February 3, 2012
• Last Verified: February 2012

Keywords provided by Takeda:

Diabetes Mellitus - Type 2; Diabetes Mellitus; Drug Therapy

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Alogliptin; Voglibose; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Glycoside Hydrolase Inhibitors