Clinical trial NCT01263483: Efficacy and Safety of Alogliptin Used in Combination With α-glucosidase Inhibitor in Participants With Type 2 Diabetes in Japan
Official title: A Phase 2/3, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Determine the Efficacy and Safety of SYR-322 When Used in Combination With α-glucosidase Inhibitor in Subjects With Type 2 Diabetes in Japan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus - Type 2
Diabetes Mellitus
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-12-20
Enrollment: 230
Sex: ALL
Minimum age (years): 33
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy and safety of alogliptin, once daily (QD) combined with an α-glucosidase inhibitor taken three times daily (TID) in type 2 diabetic patients with uncontrolled blood glucose.

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.

In Japan, α-glucosidase inhibitors are widely used as a first-line treatment for type 2 diabetes mellitus. Because alogliptin has a different mechanism of action compared to α-glucosidase inhibitors, the study evaluated the efficacy and safety of alogliptin combined with an α-glucosidase inhibitor in type 2 diabetic patients with uncontrolled blood glucose while taking a α-glucosidase inhibitor and receiving diet and/or exercise therapies.

To evaluate the long-term safety and efficacy of the concomitant use of alogliptin and an α-glucosidase inhibitor, subjects who participated in the present study could enter a long-term extension study SYR-322/OCT-003 (NCT01263509) that was planned separately.

Eligibility criteria: Inclusion Criteria:

* Had been receiving a stable dose and regimen of an α-glucosidase inhibitor for the last 4 weeks or longer before the start of the screening phase (Week -8) and during the screening phase.
* Had a glycosylated hemoglobin (HbA1c) value of 6.5% or more and below 10.0% 4 weeks after the start of the screening phase (Week -4).
* Had HbA1c differences within 10.0% at the start of the screening phase (Week -8) and 4 weeks after the start of the screening phase (Week -4) from the HbA1c value at the start of the screening phase.
* Was receiving a specific diet therapy and an exercise therapy (if any) for the last 4 weeks or longer before the start of the screening phase (Week -8).

Exclusion Criteria:

* Had received any antidiabetic drug other than α-glucosidase inhibitors within the last 4 weeks before the start of the screening phase (Week -8) or during the screening phase.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (Week 12).
timeFrame: Baseline and Week 12.
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (Week 2).
timeFrame: Baseline and Week 2.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting Plasma Glucose (Week 2).
timeFrame: Baseline and Week 2
measure: Change From Baseline in Fasting Plasma Glucose (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Fasting Plasma Glucose (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting Plasma Glucose (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Fasting C-peptide (Week 2).
timeFrame: Baseline and Week 2.
measure: Change From Baseline in Fasting C-peptide (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Fasting C-peptide (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting C-peptide (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (2-hr Postprandial Value).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Blood Glucose Measured by Meal Tolerance Testing (AUC (0-2)).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Insulin Measured by Meal Tolerance Testing (AUC(0-2).
timeFrame: Baseline and Week 12
measure: Change From Baseline in C-peptide Measured by Meal Tolerance Testing (AUC(0-2).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Glucagon Measured by Meal Tolerance Testing (AUC (0-2)).
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Kawasaki Medical School
name: Professor, Department of Medicine
role: STUDY_DIRECTOR
References:
citation: Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K. Alogliptin plus voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension. Curr Med Res Opin. 2011 Nov;27 Suppl 3:21-9. doi: 10.1185/03007995.2011.614936.