Long-term Safety Study of Alogliptin Used in Combination With Sulfonylurea or Metformin in Participants With Type 2 Diabetes in Japan

Study Overview
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Brief Summary
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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
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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. 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).

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Alogliptin and glimepiride
* Drug: Alogliptin and glimepiride
* Drug: Alogliptin and metformin
* Drug: Alogliptin and metformin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 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 Glimepiride 1- 6 mg QD or BID<br> | Drug: Alogliptin and glimepiride<br>* 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.<br>* Other names: Amaryl;|
| Active Comparator: Alogliptin 25 mg QD and Glimepiride 1 - 6 mg QD or BID<br> | Drug: Alogliptin and glimepiride<br>* 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.<br>* Other names: Amaryl;|
| Active Comparator: Alogliptin 12.5 mg QD and Metformin 500 mg BID or 750 mg TID<br> | Drug: Alogliptin and metformin<br>* 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.<br>* Other names: Glycoran;|
| Active Comparator: Alogliptin 25 mg QD and Metformin 500 mg BID or 750 mg TID<br> | Drug: Alogliptin and metformin<br>* 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.<br>* Other names: Glycoran;|

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 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. | 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 final visit and glycosylated hemoglobin collected at baseline. | Baseline and Final Visit (up to 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 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 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 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 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