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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00703755
• Date of registration: 20/06/2008
• Primary sponsor: Solvay Pharmaceuticals
• Public title: A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.
• Scientific title: A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.
• Date of first enrolment: March 2003
• Target sample size: 2288
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00703755
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Countries of recruitment

Canada, Finland, Hungary, Italy, Netherlands, Norway, Poland, Romania, Sweden

Contacts

• Name: Global Clinical Director Solvay
• Affiliation: Solvay Pharmaceuticals

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Patients With Metabolic Syndrome

Intervention(s)

Drug: Fenofibrate /Metformin

Drug: Placebo

Primary Outcome(s)

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)]

Secondary Outcome(s)

Adverse events (AEs). [Time Frame: End of study visit (V4)]

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)]

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)]

Blood pressure. [Time Frame: End of study visit (V4)]

Body mass index (BMI), waist circumference, hip circumference, waist to hip ratio, and blood pressure. [Time Frame: End of study visit (V4)]

Fasting blood insulin and fasting blood glucose, HbA1c. [Time Frame: End of study visit (V4)]

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)]

Hematology: white blood cells (WBC) and differential count, red blood cells (RBC), hemoglobin, hematocrit and platelets. [Time Frame: End of study visit (V4)]

Insulin sensitivity assessed by the OGTT-derived composite whole-body Insulin Sensitivity Index (ISI) [Time Frame: End of study visit (V4)]

Percentage of patients who presented 0, 1, 2, 3, 4 or 5 MetS criteria. [Time Frame: End of study visit (V4)]

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)]

Secondary ID(s)

CFEN0203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors