A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.

This study has been completed.
Sponsor:
Information provided by:
Solvay Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00703755
First received: June 20, 2008
Last updated: June 24, 2008
Last verified: June 2008
  Purpose

The purpose of this study was to study the effect of different combinations of fenofibrate and metformin on the cluster of metabolic syndrome (MetS) biochemical abnormalities, and to determine the dose combination allowing normalization of MetS patients.


Condition Intervention Phase
Patients With Metabolic Syndrome
Drug: Fenofibrate /Metformin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.

Resource links provided by NLM:


Further study details as provided by Solvay Pharmaceuticals:

Primary Outcome Measures:
  • The percentage of normalized patients at V4 (fasting glucose < 6.1 mmol/L, TG < 1.69 mmol/L and HDL-C >= 1.03 mmol/L in males and >= 1.29 mmol/L in females) [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fasting blood insulin and fasting blood glucose, HbA1c. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Area under the curve from 0 to 2h (AUC0-2h) of glucose, insulin, C-peptide and free fatty acids (FFA) during Oral Glucose Tolerance Test (OGTT). [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Insulin sensitivity assessed by the OGTT-derived composite whole-body Insulin Sensitivity Index (ISI) [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Fasting lipid parameters: FFA, TG, TC, HDL-C, measured LDL-C, VLDL-C, small dense LDL, apolipoprotein (Apo) A1, Apo A2, Apo CIII, LDL and HDL sizes, remna [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Plasminogen -1 Activation Inhibitor (PAI-1) activity, PAI-1 antigen, tissue-type Plasminogen Activator antigen (t-PA-ag), high sensitivity C-reactive protein (hsCRP), fibrinogen, tumor necrosing factor (TNF) alpha, interleukin (IL)1 and IL6. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Body mass index (BMI), waist circumference, hip circumference, waist to hip ratio, and blood pressure. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Percentage of patients who presented 0, 1, 2, 3, 4 or 5 MetS criteria. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Adverse events (AEs). [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Biochemistry: creatinine phosphokinase (CPK), AST, ALT, GGT, alkaline phosphatase, serum creatinine, total bilirubin, blood urea nitrogen (BUN), uric acid, albumin and total homocysteine [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Hematology: white blood cells (WBC) and differential count, red blood cells (RBC), hemoglobin, hematocrit and platelets. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]
  • Blood pressure. [ Time Frame: End of study visit (V4) ] [ Designated as safety issue: No ]

Enrollment: 2288
Study Start Date: March 2003
Study Completion Date: June 2004
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Fenofibrate /Metformin
fenofibrate 2 x 40 mg bid + metformin 850 mg bid (F160-M1700)
Experimental: 2 Drug: Fenofibrate /Metformin
fenofibrate 2 x 40 mg bid + metformin 500 mg bid (F160-M1000)
Experimental: 3 Drug: Fenofibrate /Metformin
fenofibrate 40 mg bid + metformin 850 mg bid (F80-M1700)
Experimental: 4 Drug: Fenofibrate /Metformin
fenofibrate 40 mg bid + metformin 500 mg bid (F80-M1000)
Experimental: 5 Drug: Fenofibrate /Metformin
fenofibrate 2 x 40 mg bid + metformin placebo (F160-M0)
Experimental: 6 Drug: Fenofibrate /Metformin
fenofibrate placebo + metformin 850 mg bid (F0-M1700)
Placebo Comparator: 7 Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged from 18 to 75 years old (at inclusion V1).
  • With 3 of the following 5 criteria, including at least 2 biochemical abnormalities (glucose and one lipid abnormality)
  • And having signed a written informed consent (at inclusion V1).

Exclusion Criteria:

  • known Type 1 diabetes, or treated type 2 diabetes [25], [26];

    • wth HbA1c > 8 % [27] at the first blood sample;
    • body mass index (BMI) > 45 kg/m2;
    • females who were not surgically sterilized or not using adequate contraceptive or not using adequate contraceptive precautions or not postmenopausal
    • pregnant or lactating women;
    • known hypersensitivity to fibrates;
    • known hypersensitivity to metformin chlorhydrate; known abnormal thyroid hormone levels, or high thyroid stimulating hormone (TSH) level;
    • having received an investigational drug in the last 30 days before the date of randomization;
    • unable or unwilling to comply with the protocol;
    • likely to withdraw from the study before its completion;
    • treated with some concomitant medications:
    • reporting a change within the last 6 weeks before randomization and during the study in the medications that could interfere with the lipid profile (i.e., anti-hypertensive drugs, oral corticosteroids, thyroid hormones, retinoids, thiazidic derivatives, hormone replacement therapies);
    • presenting with the following disease or conditions:

      • chronic respiratory insufficiency, patient with medical device for sleep apnea;
      • current chronic pancreatitis, or identified risk or known history of acute pancreatitis;
      • hepatic insufficiency, acute alcohol intoxication, alcoholism;
      • known cholelithiasis without cholecystectomy;
      • aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 times the upper limit normal (ULN);
      • musculoskeletal disease or increased creatine phosphokinase (CPK) > 3 times the ULN;
      • renal failure or renal dysfunction defined by serum creatinine levels > 135 μmol/L in males and > 110 μmol/L in females [28];
      • acute conditions with the potential to alter renal function such as dehydration, severe infection, shock or intravascular administration of iodinated contrast agents;
      • acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction (within 3 months prior to randomization), shock;
      • known gastric or peptic ulcer or intestinal disease within the previous 3 months of randomization capable of modifying the intestinal absorption of the drugs;
      • any other severe pathology such as cancer, mental illness, etc., which in the opinion of the investigator might pose a risk to the patient or confound the results of the study
  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: NCT00703755

  Show 101 Study Locations
Sponsors and Collaborators
Solvay Pharmaceuticals
Investigators
Study Director: Global Clinical Director Solvay Solvay Pharmaceuticals
  More Information

No publications provided

Responsible Party: Bruno Fraitag, Solvay Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00703755     History of Changes
Other Study ID Numbers: CFEN0203
Study First Received: June 20, 2008
Last Updated: June 24, 2008
Health Authority: Canada: Health Canada

Keywords provided by Solvay Pharmaceuticals:
Diabetes
Hypertriglyceridaemia
Metabolic Syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Fenofibrate
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014