Long-term Safety Study of Alogliptin in Participants With Type 2 Diabetes in Japan

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01263496
First received: December 17, 2010
Last updated: February 1, 2012
Last verified: February 2012
  Purpose

The purpose of this study was to evaluate the long-term safety and efficacy of SYR-322, once daily (QD), to an α-glucosidase inhibitor, three times daily (TID), administered for 40 consecutive weeks in participants who completed a phase 2 dose-ranging study.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Alogliptin
Drug: Voglibose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Long-term, Open-label Extension Study to Investigate the Long-term Safety of SYR-322 in Subjects With Type 2 Diabetes in Japan.

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Number of Participants With Adverse Events. [ Time Frame: 52 Weeks. ] [ Designated as safety issue: Yes ]
    A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pre-treatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug, which increases in intensity after the start of dosing. Adverse events data with onset occurring more than 30 days after last dose of study drug (AE start date - last dose date >30) will be listed, but not included in the summary tables below.


Secondary Outcome Measures:
  • Change From Baseline in Glycosylated Hemoglobin (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    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 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    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 16 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    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 20 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    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 24 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 28). [ Time Frame: Baseline and Week 28. ] [ Designated as safety issue: No ]
    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 28 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 32). [ Time Frame: Baseline and Week 32. ] [ Designated as safety issue: No ]
    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 32 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 36). [ Time Frame: Baseline and Week 36. ] [ Designated as safety issue: No ]
    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 36 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 40). [ Time Frame: Baseline and Week 40. ] [ Designated as safety issue: No ]
    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 40 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 44). [ Time Frame: Baseline and Week 44. ] [ Designated as safety issue: No ]
    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 44 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 48). [ Time Frame: Baseline and Week 48. ] [ Designated as safety issue: No ]
    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 48 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    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 52 and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Glycosylated Hemoglobin (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    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 52 or final visit and glycosylated hemoglobin collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 12). [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 24 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 28). [ Time Frame: Baseline and Week 28. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 28 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 32). [ Time Frame: Baseline and Week 32. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 32 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 36). [ Time Frame: Baseline and Week 36. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 36 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 40). [ Time Frame: Baseline and Week 40. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 40 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 44). [ Time Frame: Baseline and Week 44. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 44 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 48). [ Time Frame: Baseline and Week 48. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 48 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 52 and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting Plasma Glucose (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of fasting plasma glucose collected at week 52 or final visit and fasting plasma glucose collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 12 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 16). [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 16 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 20). [ Time Frame: Baseline and Week 20. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 20 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 24 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 28). [ Time Frame: Baseline and Week 28. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 28 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 32). [ Time Frame: Baseline and Week 32. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 32 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 36). [ Time Frame: Baseline and Week 36. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 36 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 40). [ Time Frame: Baseline and Week 40. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 40 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 44). [ Time Frame: Baseline and Week 44. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 44 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 48). [ Time Frame: Baseline and Week 48. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 48 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 52 and fasting C-peptide collected at baseline.

  • Change From Baseline in Fasting C-peptide (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of fasting C-peptide collected at week 52 or final visit and fasting C-peptide collected at baseline.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 12 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 24 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 52 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 52 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 12 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 24 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 52 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 2 hours after the start of the meal.

  • Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of blood glucose collected at week 52 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 2 hours after the start of the meal.

  • Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). [ Time Frame: Baseline and Week 12. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 12 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.

  • Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 24 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.

  • Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 52 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.

  • Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of C-peptide collected at week 52 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.

  • Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 12 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.

  • Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 24 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.

  • Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 52 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.

  • Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of insulin collected at week 52 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.

  • Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    The change between the value of glucagons collected at week 12 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.

  • Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). [ Time Frame: Baseline and Week 24. ] [ Designated as safety issue: No ]
    The change between the value of glucagons collected at week 24 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.

  • Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). [ Time Frame: Baseline and Week 52. ] [ Designated as safety issue: No ]
    The change between the value of glucagons collected at week 52 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.

  • Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). [ Time Frame: Baseline and Final Visit (up to Week 52). ] [ Designated as safety issue: No ]
    The change between the value of glucagons collected at week 52 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.


Enrollment: 438
Study Start Date: May 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alogliptin 6.25 mg QD Drug: Alogliptin
Alogliptin 6.25 mg, tablets, orally, once daily for up to 40 weeks.
Other Name: SYR-322
Experimental: Alogliptin 12.5 mg QD Drug: Alogliptin
Alogliptin 12.5 mg, tablets, orally, once daily for up to 40 weeks.
Other Name: SYR-322
Experimental: Alogliptin 25 mg QD Drug: Alogliptin
Alogliptin 25 mg, tablets, orally, once daily for up to 40 weeks.
Other Name: SYR-322
Experimental: Alogliptin 50 mg QD Drug: Alogliptin
Alogliptin 50 mg, tablets, orally, once daily for up to 40 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 40 weeks.
Other Names:
  • Voglib
  • BASEN®

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, this extension study was administered for 40 consecutive weeks (52 weeks from the start of treatment in the phase 2 dose-ranging study) to participants who had completed the phase 2 dose-ranging study SYR-322/CCT-001 (NCT01263470).

  Eligibility

Ages Eligible for Study:   29 Years to 87 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Had completed the phase 2 dose-ranging study (i.e., the subject had completed the study visit at Week 12).

Exclusion Criteria:

  • Had clinical manifestations of hepatic impairment (e.g., an aspartate aminotransferase or alanine aminotransferase value 2.5 times or more of the upper reference limit at Week 8 of treatment in the phase 2 dose-ranging study).
  • Had clinical manifestations of renal impairment (e.g., a creatinine value of 2 mg/dL or more at Week 8 of treatment in the phase 2 dose-ranging study).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263496

Sponsors and Collaborators
Takeda
Investigators
Study Director: Professor, Department of Medicine Kawasaki Medical School
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01263496     History of Changes
Other Study ID Numbers: SYR-322/OCT-001, U1111-1118-4027
Study First Received: December 17, 2010
Results First Received: June 8, 2011
Last Updated: February 1, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Takeda:
Diabetes Mellitus - Type 2
Diabetes Mellitus
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Alogliptin
Voglibose
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014