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

Diabetes Mellitus Clinical Trial

— PRISMA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00772174
• Other study ID #: IT-PIO-108
• Secondary ID: 2006-000725-54PI
• Status: Completed
• Phase: Phase 3
• First received: October 8, 2008
• Last updated: July 1, 2010
• Start date: January 2007
• Est. completion date: February 2008

Study information

• Verified date: July 2010
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Metabolic Syndrome X

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Increase in High-Density Lipoprotein cholesterol levels.		Final Visit.	No
Secondary	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).		Weeks: 8 and 24.	No
Secondary	The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (blood pressure).		At all Visits.	No
Secondary	The change from Baseline in Individual Metabolic Parameters (insulin sensitivity and beta-cell function, inflammatory cytokines, adipokines, endothelial functionality).		Weeks: 8 and 24.	No
Secondary	Adverse Events.		At all Visits.	Yes
Secondary	The change from Baseline in Laboratory Parameters (hematology, chemistry and urinalysis).		Weeks: 8 and 24.	Yes

External Links

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