Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.

Phase 3

Completed

• Conditions: Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: Alogliptin; Drug: Alogliptin and Pioglitazone

• Registration Number: NCT00655863
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to compare the efficacy of Alogliptin, once daily (QD), taken by itself and with pioglitazone on postprandial lipid measures in type 2 diabetes.

Detailed Description

SYR-322 (alogliptin) is a selective, orally available inhibitor of dipeptidyl peptidase IV being developed as a treatment for type 2 diabetes mellitus. Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide.

Pioglitazone HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan). Pioglitazone HCl depends on the presence of insulin for its mechanism of action.

This study will assess the effects of alogliptin and alogliptin coadministered with pioglitazone HCl on postprandial lipid and lipoprotein metabolism in participants with type 2 diabetes. Individuals who participate in this study will be required to commit to a screening visit and up to 6 additional visits at the study center. Study participation is anticipated to be about 20 weeks (or approximately 5 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms. At 3 of the visits a meal will be served that must be eaten within 10 minutes.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2008-04-04
• Study First Submitted QC: 2008-04-09
• Study First Posted: 2008-04-10
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Results First Submitted: 2013-02-17
• Status Verified: 2013-05
• Results First Submitted QC: 2013-05-23
• Last Update Submitted: 2013-05-23
• Results First Posted: 2013-05-27
• Last Update Posted: 2013-05-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo QD	Placebo	-
Alogliptin 25 mg QD	Alogliptin	-
Alogliptin 25 mg QD + Pioglitazone 30 mg QD	Alogliptin and Pioglitazone	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16.	Baseline and Week 16.	The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Postprandial Proinsulin	Baseline, Week 4 and Week 16.	The change in postprandial proinsulin collected at each week indicated relative to baseline.
Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1)	Baseline, Week 4 and Week 16.	Postprandial changes over time at each week indicated relative to baseline.
Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4.	Baseline and Week 4.	The change in postprandial incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8h)) postdose at week 4 relative to baseline.
Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters.	Baseline, Week 4 and Week 16.	The change in postprandial incremental area under the plasma concentration-time curve for very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL2 cholesterol, VLDL2 triglycerides, chylomicron cholesterol, chylomicron triglycerides, intermediate-density lipoprotein (IDL) cholesterol, and IDL triglycerides from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.
Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters.	Baseline, Week 4 and Week 16.	Postprandial incremental area under the curve changes for very-low-density lipoprotein (VLDL) Apo B-48, VLDL Apo B 100, VLDL2 Apo B-48, VLDL2 Apo B 100, chylomicron Apo B-48, chylomicron Apo B 100, and intermediate density lipoprotein (IDL) Apo B-48, IDL Apo B 100, and triglyceride-rich remnant (TRR) lipoproteins from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.
Postprandial Changes Over Time From Baseline for Glucose	Baseline, Week 4 and Week 16.	Postprandial changes over time at each week indicated relative to baseline.
Postprandial Changes Over Time From Baseline for Insulin	Baseline, Week 4 and Week 16.	Postprandial changes over time at each week indicated relative to baseline.
Postprandial Changes Over Time From Baseline for Glucagon	Baseline, Week 4 and Week 16.	Postprandial changes over time at each week indicated relative to baseline.
Change From Baseline in Glycosylated Hemoglobin	Baseline, Week 8 and 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 each week indicated relative to baseline.
Change From Baseline in Fasting Plasma Glucose	Baseline, Week 4, Week 8 and Week 16.	The change in fasting plasma glucose collected at each week indicated relative to baseline.
Change From Baseline in Postprandial C-Peptide	Baseline, Week 4 and Week 16.	The change in postprandial C-peptide collected at each week indicated relative to baseline.
Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP)	Baseline, Week 4 and Week 16.	The change in hs-CRP collected at each week indicated relative to baseline.
Change From Baseline in Adiponectin	Baseline, Week 4 and Week 16.	The change in adiponectin collected at each week indicated relative to baseline.
Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM)	Baseline, Week 4 and Week 16.	The change in VCAM collected at each week indicated relative to baseline.
Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM)	Baseline, Week 4 and Week 16.	The change in ICAM collected at each week indicated relative to baseline.
Change From Baseline in e-Selectin	Baseline, Week 4 and Week 16.	The change in e-Selectin collected at each week indicated relative to baseline.
Change From Baseline in Endothelial Function Through Pulse Wave Tonometry	Baseline and Week 16.	Pulse wave tonometry performed before the meal and 2 hours postmeal using one recording consisting of 15 to 20 sequentially recorded radial artery waveforms collected at each assessment.