Back to resultsLong-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Alogliptin and glimepiride
Alogliptin and glimepiride
Alogliptin and metformin
Alogliptin and metformin
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Diabetes Mellitus - Type 2, Diabetes Mellitus, Drug Therapy
Eligibility Criteria
Inclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
- Had completed the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study.
- Was capable of understanding and complying with protocol requirements.
- Signed a written informed consent form prior to the initiation of any study procedure.
Exclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
- With clinical manifestation of hepatic impairment (eg, an aspartate aminotransferase or alanine aminotransferase value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
- With clinical manifestation of renal impairment (eg, a creatinine value of 1.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
- With serious cardiac disease, cerebrovascular disorder, or serious pancreatic or hematological disease (eg, a subject who requires hospital admission).
Criteria that applied only to participants completing the core phase 2/3 metformin add-on study:
1. With history or symptoms of lactic acidosis.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID
Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID
Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID
Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events.
Treatment-emergent adverse events (TEAE) are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
Secondary Outcome Measures
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.
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 and glycosylated hemoglobin collected at baseline.
Change From Baseline in Glycosylated Hemoglobin (Week 16).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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 final visit and glycosylated hemoglobin collected at baseline.
Change From Baseline in Fasting Blood Glucose (Week 8).
The change between the value of fasting blood glucose collected at week 8 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 12).
The change between the value of fasting blood glucose collected at week 12 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 16).
The change between the value of fasting blood glucose collected at week 6 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 20).
The change between the value of fasting blood glucose collected at week 20 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 24).
The change between the value of fasting blood glucose collected at week 24 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 28).
The change between the value of fasting blood glucose collected at week 28 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 32).
The change between the value of fasting blood glucose collected at week 32 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 36).
The change between the value of fasting blood glucose collected at week 36 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 40).
The change between the value of fasting blood glucose collected at week 40 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 44).
The change between the value of fasting blood glucose collected at week 44 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 48).
The change between the value of fasting blood glucose collected at week 48 and baseline.
Change From Baseline in Fasting Blood Glucose (Week 52).
The change between the value of fasting blood glucose collected at week 52 and baseline.
Change From Baseline in Fasting Blood Glucose (Final Visit).
The change between the value of fasting blood glucose collected at final visit and baseline.
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 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 Blood Glucose Measured by the Meal Tolerance Test (Week 24).
The change between the value of blood glucose measured by the meal tolerance test collected at week 24 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 Blood Glucose Measured by the Meal Tolerance Test (Week 52).
The change between the value of blood glucose measured by the meal tolerance test collected at week 52 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 Blood Glucose Measured by the Meal Tolerance Test (Final Visit).
The change between the value of blood glucose measured by the meal tolerance test collected at 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01318135
Brief Title
Long-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan
Official Title
A Long-term, Open-label Extension Study to Investigate the Long-term Safety of Alogliptin When Used in Combination With Sulfonylurea or Metformin in Subjects With Type 2 Diabetes in Japan
Study Type
Interventional
2. Study Status
Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
April 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the efficacy and safety of alogliptin administered as an add-on to sulfonylurea (glimepiride) or metformin, once daily (QD), twice daily (BID) or three times daily (TID).
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.
This was a phase 2/3, multicenter, open-label study, in participants who had completed the core phase 2/3 sulfonylurea add-on study (SYR-322/CCT-005; NCT01318083) or the core phase 2/3 metformin add-on study (SYR-322/CCT-006; NCT01318109) to evaluate the safety and efficacy of alogliptin administered as an add-on to a sulfonylurea (glimepiride) or metformin continuously for 40 weeks (52 weeks from the start of study treatment with alogliptin in the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Diabetes Mellitus - Type 2, Diabetes Mellitus, Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
576 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alogliptin 12.5 mg QD and Glimepiride 1- 6 mg QD or BID
Arm Type
Active Comparator
Arm Title
Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID
Arm Type
Active Comparator
Arm Title
Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID
Arm Type
Active Comparator
Arm Title
Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Alogliptin and glimepiride
Other Intervention Name(s)
SYR-322, Amaryl
Intervention Description
Alogliptin 12.5 mg, tablets, orally, once daily and sulfonylurea 1, 2, 3, 4, 5 or 6 mg, tablets, orally, once or twice daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Alogliptin and glimepiride
Other Intervention Name(s)
SYR-322, Amaryl
Intervention Description
Alogliptin 25 mg, tablets, orally, once daily and sulfonylurea 1, 2, 3, 4, 5 or 6 mg, tablets, orally, once or twice daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Alogliptin and metformin
Other Intervention Name(s)
SYR-322, Glycoran
Intervention Description
Alogliptin 12.5 mg, tablets, orally, once daily and metformin 500 mg, tablets, orally, twice daily or metformin 750 mg, tablets, orally, three times daily for up to 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Alogliptin and metformin
Other Intervention Name(s)
SYR-322, Glycoran
Intervention Description
Alogliptin 25 mg, tablets, orally, once daily and metformin 500 mg, tablets, orally, twice daily or metformin 750 mg, tablets, orally, three times daily for up to 52 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events.
Description
Treatment-emergent adverse events (TEAE) are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
Time Frame
52 Weeks.
Secondary Outcome Measure Information:
Title
Change From Baseline in Glycosylated Hemoglobin (Week 8).
Description
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.
Time Frame
Baseline and Week 8.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 12).
Description
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.
Time Frame
Baseline and Week 12.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 16).
Description
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.
Time Frame
Baseline and Week 16.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 20).
Description
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.
Time Frame
Baseline and Week 20.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 24).
Description
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.
Time Frame
Baseline and Week 24.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 28).
Description
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.
Time Frame
Baseline and Week 28.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 32).
Description
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.
Time Frame
Baseline and Week 32.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 36).
Description
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.
Time Frame
Baseline and Week 36.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 40).
Description
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.
Time Frame
Baseline and Week 40.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 44).
Description
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.
Time Frame
Baseline and Week 44.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 48).
Description
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.
Time Frame
Baseline and Week 48.
Title
Change From Baseline in Glycosylated Hemoglobin (Week 52).
Description
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.
Time Frame
Baseline and Week 52.
Title
Change From Baseline in Glycosylated Hemoglobin (Final Visit).
Description
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 final visit and glycosylated hemoglobin collected at baseline.
Time Frame
Baseline and Final Visit (up to 52).
Title
Change From Baseline in Fasting Blood Glucose (Week 8).
Description
The change between the value of fasting blood glucose collected at week 8 and baseline.
Time Frame
Baseline and Week 8.
Title
Change From Baseline in Fasting Blood Glucose (Week 12).
Description
The change between the value of fasting blood glucose collected at week 12 and baseline.
Time Frame
Baseline and Week 12.
Title
Change From Baseline in Fasting Blood Glucose (Week 16).
Description
The change between the value of fasting blood glucose collected at week 6 and baseline.
Time Frame
Baseline and Week 16.
Title
Change From Baseline in Fasting Blood Glucose (Week 20).
Description
The change between the value of fasting blood glucose collected at week 20 and baseline.
Time Frame
Baseline and Week 20.
Title
Change From Baseline in Fasting Blood Glucose (Week 24).
Description
The change between the value of fasting blood glucose collected at week 24 and baseline.
Time Frame
Baseline and Week 24.
Title
Change From Baseline in Fasting Blood Glucose (Week 28).
Description
The change between the value of fasting blood glucose collected at week 28 and baseline.
Time Frame
Baseline and Week 28.
Title
Change From Baseline in Fasting Blood Glucose (Week 32).
Description
The change between the value of fasting blood glucose collected at week 32 and baseline.
Time Frame
Baseline and Week 32.
Title
Change From Baseline in Fasting Blood Glucose (Week 36).
Description
The change between the value of fasting blood glucose collected at week 36 and baseline.
Time Frame
Baseline and Week 36.
Title
Change From Baseline in Fasting Blood Glucose (Week 40).
Description
The change between the value of fasting blood glucose collected at week 40 and baseline.
Time Frame
Baseline and Week 40.
Title
Change From Baseline in Fasting Blood Glucose (Week 44).
Description
The change between the value of fasting blood glucose collected at week 44 and baseline.
Time Frame
Baseline and Week 44.
Title
Change From Baseline in Fasting Blood Glucose (Week 48).
Description
The change between the value of fasting blood glucose collected at week 48 and baseline.
Time Frame
Baseline and Week 48.
Title
Change From Baseline in Fasting Blood Glucose (Week 52).
Description
The change between the value of fasting blood glucose collected at week 52 and baseline.
Time Frame
Baseline and Week 52.
Title
Change From Baseline in Fasting Blood Glucose (Final Visit).
Description
The change between the value of fasting blood glucose collected at final visit and baseline.
Time Frame
Baseline and Final Visit (up to Week 52).
Title
Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 12).
Description
The change between the value of blood glucose measured by the meal tolerance test collected at week 12 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.
Time Frame
Baseline and Week 12.
Title
Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 24).
Description
The change between the value of blood glucose measured by the meal tolerance test collected at week 24 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.
Time Frame
Baseline and Week 24.
Title
Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Week 52).
Description
The change between the value of blood glucose measured by the meal tolerance test collected at week 52 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.
Time Frame
Baseline and Week 52.
Title
Change From Baseline in Blood Glucose Measured by the Meal Tolerance Test (Final Visit).
Description
The change between the value of blood glucose measured by the meal tolerance test collected at 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.
Time Frame
Baseline and Final Visit (up to Week 52).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
Had completed the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study.
Was capable of understanding and complying with protocol requirements.
Signed a written informed consent form prior to the initiation of any study procedure.
Exclusion Criteria:
Common criteria that applied to participants completing both the core phase 2/3 sulfonylurea add-on study and those completing the core phase 2/3 metformin add-on study:
With clinical manifestation of hepatic impairment (eg, an aspartate aminotransferase or alanine aminotransferase value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
With clinical manifestation of renal impairment (eg, a creatinine value of 1.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 sulfonylurea add-on study or the core phase 2/3 metformin add-on study).
With serious cardiac disease, cerebrovascular disorder, or serious pancreatic or hematological disease (eg, a subject who requires hospital admission).
Criteria that applied only to participants completing the core phase 2/3 metformin add-on study:
1. With history or symptoms of lactic acidosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Professor, Diabetes and Endocrine Division
Organizational Affiliation
Department of Medicine, Kawasaki Medical School
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
24843617
Citation
Seino Y, Hiroi S, Hirayama M, Kaku K. Efficacy and safety of alogliptin added to sulfonylurea in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study. J Diabetes Investig. 2012 Dec 20;3(6):517-25. doi: 10.1111/j.2040-1124.2012.00226.x. Epub 2012 Jul 12.
Results Reference
derived
Learn more about this trial
Long-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan
We'll reach out to this number within 24 hrs