Long-term Safety Study of Alogliptin Used in Combination With Thiazolidine 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 alogliptin and Thiazolidine administered once daily (QD) for 40 consecutive weeks in participants who completed a phase 2/3 Thiazolidine add on 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, participants in the present study were enrolled from a core phase 2/3 thiazolidine add on study (SYR-322/CCT-004; NCT01318070).

Official Title
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A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR-322 When Used in Combination With Thiazolidine 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 and pioglitazone
* Drug: Alogliptin and pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Had completed the core phase 2/3 thiazolidine add on study. The subject 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: With clinical manifestation of hepatic impairment (e.g., an AST or ALT value of 2.5 times or more of the upper reference limit at Week 8 of the core phase 2/3 thiazolidine add on study). With clinical manifestation of renal impairment (e.g., a creatinine value of 2 mg/dL or more at Week 8 of the core phase 2/3 thiazolidine add on study). With a history or symptoms of cardiac failure.

Ages Eligible for Study
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Minimum Age: 33 Years
Maximum Age: 88 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 |
| --- | --- |
| Active Comparator: Alogliptin 12.5 mg QD and Pioglitazone 15 or 30 mg QD<br> | Drug: Alogliptin and pioglitazone<br>* Alogliptin 12.5 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: Actos;|
| Active Comparator: Alogliptin 25 mg QD and Pioglitazone 15 or 30 mg QD<br> | Drug: Alogliptin and pioglitazone<br>* Alogliptin 25 mg, tablets, orally, once daily and Pioglitazone 15 mg or 30 mg, tablets, orally, once daily for up to 40 weeks.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events. | Treatment-emergent adverse events (TEAE) are adverse events 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 that increases in severity after the start of dosing. | 52 Weeks. | 

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 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 Blood Glucose (Week 8). | The change between the value of fasting blood glucose collected at week 8 and baseline. | Baseline and Week 8. | 
| Change From Baseline in Fasting Blood Glucose (Week 12). | The change between the value of fasting blood glucose collected at week 12 and baseline. | Baseline and Week 12. | 
| Change From Baseline in Fasting Blood Glucose (Week 16). | The change between the value of fasting blood glucose collected at week 6 and baseline. | Baseline and Week 16. | 
| Change From Baseline in Fasting Blood Glucose (Week 20). | The change between the value of fasting blood glucose collected at week 20 and baseline. | Baseline and Week 20. | 
| Change From Baseline in Fasting Blood Glucose (Week 24). | The change between the value of fasting blood glucose collected at week 24 and baseline. | Baseline and Week 24. | 
| Change From Baseline in Fasting Blood Glucose (Week 28). | The change between the value of fasting blood glucose collected at week 28 and baseline. | Baseline and Week 28. | 
| Change From Baseline in Fasting Blood Glucose (Week 32). | The change between the value of fasting blood glucose collected at week 32 and baseline. | Baseline and Week 32. | 
| Change From Baseline in Fasting Blood Glucose (Week 36). | The change between the value of fasting blood glucose collected at week 36 and baseline. | Baseline and Week 36. | 
| Change From Baseline in Fasting Blood Glucose (Week 40). | The change between the value of fasting blood glucose collected at week 40 and baseline. | Baseline and Week 40. | 
| Change From Baseline in Fasting Blood Glucose (Week 44). | The change between the value of fasting blood glucose collected at week 44 and baseline. | Baseline and Week 44. | 
| Change From Baseline in Fasting Blood Glucose (Week 48). | The change between the value of fasting blood glucose collected at week 48 and baseline. | Baseline and Week 48. | 
| Change From Baseline in Fasting Blood Glucose (Week 52). | The change between the value of fasting blood glucose collected at week 52 and baseline. | Baseline and Week 52. | 
| Change From Baseline in Fasting Blood Glucose (Final Visit). | The change between the value of fasting blood glucose collected at week 52 or final visit and baseline. | Baseline and Final Visit (up to Week 52). | 
| 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. | Baseline and Week 12. | 
| 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. | Baseline and Week 24. | 
| 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 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 52. | 
| 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 week 52 or end of study 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 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