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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00655863
First received: April 4, 2008
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Alogliptin and Pioglitazone
Drug: Alogliptin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16. [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4. [ Time Frame: Baseline and Week 4. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    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 Glucagon-like Peptide-1 (GLP-1) [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    Postprandial changes over time at each week indicated relative to baseline.

  • Postprandial Changes Over Time From Baseline for Glucose [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    Postprandial changes over time at each week indicated relative to baseline.

  • Postprandial Changes Over Time From Baseline for Insulin [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    Postprandial changes over time at each week indicated relative to baseline.

  • Postprandial Changes Over Time From Baseline for Glucagon [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    Postprandial changes over time at each week indicated relative to baseline.

  • Change From Baseline in Glycosylated Hemoglobin [ Time Frame: Baseline, Week 8 and Week 16. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 4, Week 8 and Week 16. ] [ Designated as safety issue: No ]
    The change in fasting plasma glucose collected at each week indicated relative to baseline.

  • Change From Baseline in Postprandial C-Peptide [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in postprandial C-peptide collected at each week indicated relative to baseline.

  • Change From Baseline in Postprandial Proinsulin [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in postprandial proinsulin collected at each week indicated relative to baseline.

  • Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in hs-CRP collected at each week indicated relative to baseline.

  • Change From Baseline in Adiponectin [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in adiponectin collected at each week indicated relative to baseline.

  • Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in VCAM collected at each week indicated relative to baseline.

  • Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in ICAM collected at each week indicated relative to baseline.

  • Change From Baseline in e-Selectin [ Time Frame: Baseline, Week 4 and Week 16. ] [ Designated as safety issue: No ]
    The change in e-Selectin collected at each week indicated relative to baseline.

  • Change From Baseline in Endothelial Function Through Pulse Wave Tonometry [ Time Frame: Baseline and Week 16. ] [ Designated as safety issue: No ]
    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.


Enrollment: 71
Study Start Date: July 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo QD Drug: Placebo
Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.
Other Names:
  • Actos
  • AD-4833
  • SYR-322
Experimental: Alogliptin 25 mg QD Drug: Alogliptin
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks.
Other Names:
  • alogliptin
  • SYR110322
  • SYR-322
Experimental: Alogliptin 25 mg QD + Pioglitazone 30 mg QD Drug: Alogliptin and Pioglitazone
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks.
Other Names:
  • alogliptin
  • SYR110322
  • Actos
  • AD-4833
  • SYR-322

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00655863

Locations
Netherlands
Amsterdam, Netherlands
Sweden
Gothenburg, Sweden
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
Publications:
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00655863     History of Changes
Other Study ID Numbers: SYR-322_301, 2007-000486-38, U1111-1113-2081, NL22649.029.08
Study First Received: April 4, 2008
Results First Received: February 17, 2013
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration
Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Lipoatrophic; Dyslipidemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Alogliptin
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014