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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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A Long-term, Open-label Extension Study to Investigate the Long-term Safety of SYR-322 in Subjects With Type 2 Diabetes in Japan.

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Alogliptin
* Drug: Voglibose


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 29 Years
Maximum Age: 87 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alogliptin 6.25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 6.25 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: SYR-322;|
| Experimental: Alogliptin 12.5 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 12.5 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: SYR-322;|
| Experimental: Alogliptin 25 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 25 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: SYR-322;|
| Experimental: Alogliptin 50 mg QD<br> | Drug: Alogliptin<br>* Alogliptin 50 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: SYR-322;|
| Active Comparator: Voglibose 0.2-mg TID<br> | Drug: Voglibose<br>* Voglibose 0.2 mg, tablets, orally, three times daily for up to 40 weeks.<br>* Other names: BASEN®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events. | 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. | 52 Weeks. | 

Secondary 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 and glycosylated hemoglobin collected at baseline. | Baseline and Week 12. | 
| 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. | Baseline and Week 16. | 
| 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. | Baseline and Week 20. | 
| 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. | Baseline and Week 24. | 
| 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. | Baseline and Week 28. | 
| 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. | Baseline and Week 32. | 
| 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. | Baseline and Week 36. | 
| 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. | Baseline and Week 40. | 
| 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. | Baseline and Week 44. | 
| 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. | Baseline and Week 48. | 
| 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. | Baseline and Week 52. | 
| 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 week 52 or final visit and glycosylated hemoglobin collected at baseline. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Fasting Plasma Glucose (Week 12). | The change between the value of fasting plasma glucose collected at week 12 and fasting plasma glucose collected at baseline. | Baseline and Week 12 | 
| Change From Baseline in Fasting Plasma Glucose (Week 16). | The change between the value of fasting plasma glucose collected at week 16 and fasting plasma glucose collected at baseline. | Baseline and Week 16. | 
| Change From Baseline in Fasting Plasma Glucose (Week 20). | The change between the value of fasting plasma glucose collected at week 20 and fasting plasma glucose collected at baseline. | Baseline and Week 20. | 
| Change From Baseline in Fasting Plasma Glucose (Week 24). | The change between the value of fasting plasma glucose collected at week 24 and fasting plasma glucose collected at baseline. | Baseline and Week 24. | 
| Change From Baseline in Fasting Plasma Glucose (Week 28). | The change between the value of fasting plasma glucose collected at week 28 and fasting plasma glucose collected at baseline. | Baseline and Week 28. | 
| Change From Baseline in Fasting Plasma Glucose (Week 32). | The change between the value of fasting plasma glucose collected at week 32 and fasting plasma glucose collected at baseline. | Baseline and Week 32. | 
| Change From Baseline in Fasting Plasma Glucose (Week 36). | The change between the value of fasting plasma glucose collected at week 36 and fasting plasma glucose collected at baseline. | Baseline and Week 36. | 
| Change From Baseline in Fasting Plasma Glucose (Week 40). | The change between the value of fasting plasma glucose collected at week 40 and fasting plasma glucose collected at baseline. | Baseline and Week 40. | 
| Change From Baseline in Fasting Plasma Glucose (Week 44). | The change between the value of fasting plasma glucose collected at week 44 and fasting plasma glucose collected at baseline. | Baseline and Week 44. | 
| Change From Baseline in Fasting Plasma Glucose (Week 48). | The change between the value of fasting plasma glucose collected at week 48 and fasting plasma glucose collected at baseline. | Baseline and Week 48. | 
| Change From Baseline in Fasting Plasma Glucose (Week 52). | The change between the value of fasting plasma glucose collected at week 52 and fasting plasma glucose collected at baseline. | Baseline and Week 52. | 
| Change From Baseline in Fasting Plasma Glucose (Final Visit). | The change between the value of fasting plasma glucose collected at week 52 or final visit and fasting plasma glucose collected at baseline. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Fasting C-peptide (Week 12). | The change between the value of fasting C-peptide collected at week 12 and fasting C-peptide collected at baseline. | Baseline and Week 12. | 
| Change From Baseline in Fasting C-peptide (Week 16). | The change between the value of fasting C-peptide collected at week 16 and fasting C-peptide collected at baseline. | Baseline and Week 16. | 
| Change From Baseline in Fasting C-peptide (Week 20). | The change between the value of fasting C-peptide collected at week 20 and fasting C-peptide collected at baseline. | Baseline and Week 20. | 
| Change From Baseline in Fasting C-peptide (Week 24). | The change between the value of fasting C-peptide collected at week 24 and fasting C-peptide collected at baseline. | Baseline and Week 24. | 
| Change From Baseline in Fasting C-peptide (Week 28). | The change between the value of fasting C-peptide collected at week 28 and fasting C-peptide collected at baseline. | Baseline and Week 28. | 
| Change From Baseline in Fasting C-peptide (Week 32). | The change between the value of fasting C-peptide collected at week 32 and fasting C-peptide collected at baseline. | Baseline and Week 32. | 
| Change From Baseline in Fasting C-peptide (Week 36). | The change between the value of fasting C-peptide collected at week 36 and fasting C-peptide collected at baseline. | Baseline and Week 36. | 
| Change From Baseline in Fasting C-peptide (Week 40). | The change between the value of fasting C-peptide collected at week 40 and fasting C-peptide collected at baseline. | Baseline and Week 40. | 
| Change From Baseline in Fasting C-peptide (Week 44). | The change between the value of fasting C-peptide collected at week 44 and fasting C-peptide collected at baseline. | Baseline and Week 44. | 
| Change From Baseline in Fasting C-peptide (Week 48). | The change between the value of fasting C-peptide collected at week 48 and fasting C-peptide collected at baseline. | Baseline and Week 48. | 
| Change From Baseline in Fasting C-peptide (Week 52). | The change between the value of fasting C-peptide collected at week 52 and fasting C-peptide collected at baseline. | Baseline and Week 52. | 
| Change From Baseline in Fasting C-peptide (Final Visit). | The change between the value of fasting C-peptide collected at week 52 or final visit and fasting C-peptide collected at baseline. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 12). | 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. | Baseline and Week 12. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 24). | 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. | Baseline and Week 24. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Week 52). | 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. | Baseline and Week 52. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value) (Final Visit). | 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. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). | 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. | Baseline and Week 12. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). | 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. | Baseline and Week 24. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). | 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. | Baseline and Week 52. | 
| Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). | 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. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). | 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. | Baseline and Week 12. | 
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). | 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. | Baseline and Week 24. | 
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). | 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. | Baseline and Week 52. | 
| Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). | 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. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 12). | 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. | Baseline and Week 12 | 
| Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 24). | 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. | Baseline and Week 24. | 
| Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Week 52). | 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. | Baseline and Week 52. | 
| Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2)) (Final Visit). | 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. | Baseline and Final Visit (up to Week 52). | 
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 12). | 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. | Baseline and Week 12 | 
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 24). | 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. | Baseline and Week 24. | 
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Week 52). | 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. | Baseline and Week 52. | 
| Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)) (Final Visit). | 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. | Baseline and Final Visit (up to Week 52). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus - Type 2, Diabetes Mellitus, Drug Therapy