Efficacy and Safety Study of Pioglitazone Combined With Metformin on Metabolic Syndrome in Subjects With Type 2 Diabetes (PRISMA)

This study has been completed.
Sponsor:
Information provided by:
Takeda
ClinicalTrials.gov Identifier:
NCT00772174
First received: October 8, 2008
Last updated: July 1, 2010
Last verified: July 2010
  Purpose

The purpose of this study was to determine the efficacy of pioglitazone taken with metformin on high-density lipoprotein cholesterol in subjects with Type 2 Diabetes.


Condition Intervention Phase
Diabetes Mellitus
Drug: Pioglitazone and Metformin
Drug: Metformin
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: Double-blind, Randomized, Multicenter, Parallel-Group Study to Evaluate the Effects of Pioglitazone on Metabolic Syndrome in Patients With Type 2 Diabetes Treated With Metformin

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Increase in High-Density Lipoprotein cholesterol levels. [ Time Frame: Final Visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (aggregate waist circumference, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol). [ Time Frame: Weeks: 8 and 24. ] [ Designated as safety issue: No ]
  • The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (blood pressure). [ Time Frame: At all Visits. ] [ Designated as safety issue: No ]
  • The change from Baseline in Individual Metabolic Parameters (insulin sensitivity and beta-cell function, inflammatory cytokines, adipokines, endothelial functionality). [ Time Frame: Weeks: 8 and 24. ] [ Designated as safety issue: No ]
  • Adverse Events. [ Time Frame: At all Visits. ] [ Designated as safety issue: Yes ]
  • The change from Baseline in Laboratory Parameters (hematology, chemistry and urinalysis). [ Time Frame: Weeks: 8 and 24. ] [ Designated as safety issue: Yes ]

Enrollment: 418
Study Start Date: January 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone + Metformin Drug: Pioglitazone and Metformin
Pioglitazone 15 mg, tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone 15 mg, tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.
Other Names:
  • ACTOS®
  • AD4833
Active Comparator: Metformin Drug: Metformin
Pioglitazone placebo-matching tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone placebo-matching tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.

Detailed Description:

Diabetes is none of the most common, chronic diseases worldwide and affects nearly 200 million people. It is the fourth or fifth leading cause of death in developed countries, and it is expected that diabetes will reach epidemic proportions, affecting 333 million people globally by 2025.

The metabolic syndrome is a cluster of the most dangerous cardiovascular risk factors and includes diabetes and pre-diabetes in addition to abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides and hypertension. It is estimated that around a quarter of the world's adult population has metabolic syndrome, and are twice as likely to die and three times as likely to have a heart attack or stroke when compared to people without the syndrome. In addition, non-diabetic people with metabolic syndrome have a fivefold greater risk of developing type 2 diabetes. The clustering of cardiovascular risk factors that typifies the metabolic syndrome is now considered the driving force for a cardiovascular disease epidemic.

Metabolic syndrome has been recently defined by a Consensus Conference of the International Diabetes Federation as a cluster of clinical and laboratory signs characterized by the presence of abnormal deposition of fat tissue in the abdomen and visceral districts, and at least two other clinical and laboratory abnormalities, including altered glucose metabolism or type 2 diabetes and decreased levels of high-density lipoprotein cholesterol. One of the underlying pathophysiological mechanisms of metabolic syndrome is insulin resistance, characterized by an increased glucose output from the liver, and reduced glucose uptake in the muscle and adipose tissue cells. Drugs whose mechanism of action consists of increasing insulin sensitivity in the target tissues are able to reduce the clinical manifestations and consequences of metabolic syndrome.

While each individual component of metabolic syndrome confers an increased risk of cardiovascular-related complications or death, this risk is more pronounced when the syndrome itself is present. The more components of metabolic syndrome are evident, the higher is the cardiovascular mortality rate.

  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Type 2 Diabetes Mellitus.
  • Has glycosylated hemoglobin levels between 6.0% and 8.0%.
  • Treatment with metformin (2,000 to 3,000 mg daily) for at least 3 months.
  • Has reduced high-density lipoprotein cholesterol levels less than 40 mg/dl in males and less than 50 mg/dl in females, irrespective of treatment with statins.
  • Has central obesity defined as a waist circumference greater than or equal to 94 cm for men and greater than or equal to 80 cm for females.
  • 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.

Exclusion Criteria:

  • Has a diagnosis of Type 1 Diabetes Mellitus.
  • Required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

    • other oral antidiabetic drugs than metformin or with insulin in the 3 months preceding study entry.
    • Fibrates
    • Rifampicin
  • Has any disease with malabsorption.
  • Has acute or chronic pancreatitis.
  • Has familial polyposis coli.
  • Has a medical history of myocardial infarction, transient ischemic attacks or stroke in the past 6 months.
  • Has heart failure as defined by the New York Heart Association classification I-IV.
  • Has significant liver impairment, with an alanine aminotransferase level greater than 2.5 the upper limit of normal range.
  • Has significant renal impairment, with a serum creatinine level greater than 1.5 mg/dl for men and greater than 1.2 mg/dl for women.
  • Has anemia of any etiology (defined as hemoglobin levels less than 10.5 g/dL) or any other hematologic disease.
  • Has a diagnosis or suspicion of neoplastic disease.
  • History of chronic alcohol or drug abuse.
  • Known allergy, sensitivity or intolerance to the study drugs and their formulation ingredients.
  • Participation in another trial in the 3 months preceding study entry.
  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: NCT00772174

Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Medical Director, Takeda Italia Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT00772174     History of Changes
Other Study ID Numbers: IT-PIO-108, 2006-000725-54, PIOc/LAN07/TIF, U1111-1115-9278
Study First Received: October 8, 2008
Last Updated: July 1, 2010
Health Authority: Italy: The Italian Medicines Agency

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
Syndrome
Metabolic Syndrome X
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Pioglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014