Clinical trial NCT00655863: Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.
Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing SYR-322 Alone and Combination SYR-322 With Pioglitazone Versus Placebo on Postprandial Lipids in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Keywords: Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Lipoatrophic; Dyslipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-04-10
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

* Diagnosis of type 2 diabetes
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
* Either failed treatment with diet and exercise for 3 months prior to Screening or has been receiving a stable dose of metformin, sulfonylurea, nateglinide, or repaglinide for more than 3 months prior to Screening.
* Inadequate glycemic control as defined by glycosylated hemoglobin concentration between 6.5 and 9.0%, inclusive.
* Fasting plasma glucose less than 13.3 mmol per L.
* Fasting serum triglyceride level of 1.7 to 5.0 mmol per L, inclusive.
* Has not been receiving any lipid-lowering therapy within 3 months prior to Screening or on a stable statin and/or ezetimibe therapy (same drug and dose) for at least 3 months.
* Body mass index greater than 23 kg/m2 and less than 45 kg/m2.
* If has regular use of other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. Use of as needed prescription medications and over-the-counter medications is allowed at the discretion of the investigator.
* Is to be Apolipoprotein E 3/3 or Apolipoprotein E 3/4 phenotype positive prior to baseline.

Exclusion Criteria

* History of type 1 diabetes.
* History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.
* Diastolic blood pressure greater than 100 mm Hg or a systolic blood pressure of greater than 160 mm Hg.
* History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.
* Hemoglobin less than 120 g per L for males and less than100 g per L for females.
* Alanine transaminase level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
* Serum creatinine level greater than 133 μmol per L.
* Fasting total cholesterol greater than 6.5 mmol per L.
* New York Heart Association heart failure of any Class (I-IV) regardless of therapy.
* History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
* History of acute metabolic diabetic complications.
* History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
* History of infection with human immunodeficiency virus.
* History of diabetic gastro paresis.
* History of gastric bypass surgery.

Primary outcomes:
measure: Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16.
timeFrame: Baseline and Week 16.
Secondary outcomes:
measure: Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4.
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters.
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters.
timeFrame: Baseline, Week 4 and Week 16.
measure: Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1)
timeFrame: Baseline, Week 4 and Week 16.
measure: Postprandial Changes Over Time From Baseline for Glucose
timeFrame: Baseline, Week 4 and Week 16.
measure: Postprandial Changes Over Time From Baseline for Insulin
timeFrame: Baseline, Week 4 and Week 16.
measure: Postprandial Changes Over Time From Baseline for Glucagon
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Glycosylated Hemoglobin
timeFrame: Baseline, Week 8 and Week 16.
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline, Week 4, Week 8 and Week 16.
measure: Change From Baseline in Postprandial C-Peptide
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Postprandial Proinsulin
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP)
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Adiponectin
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM)
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM)
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in e-Selectin
timeFrame: Baseline, Week 4 and Week 16.
measure: Change From Baseline in Endothelial Function Through Pulse Wave Tonometry
timeFrame: Baseline and Week 16.
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
city: Gothenburg
country: Sweden
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Eliasson B, Moller-Goede D, Eeg-Olofsson K, Wilson C, Cederholm J, Fleck P, Diamant M, Taskinen MR, Smith U. Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study. Diabetologia. 2012 Apr;55(4):915-25. doi: 10.1007/s00125-011-2447-3. Epub 2012 Jan 12.