A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.
- Conditions
- Patients With Metabolic Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT00703755
- Lead Sponsor
- Solvay Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2288
- 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).
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description 1 Fenofibrate /Metformin - 2 Fenofibrate /Metformin - 3 Fenofibrate /Metformin - 4 Fenofibrate /Metformin - 5 Fenofibrate /Metformin - 6 Fenofibrate /Metformin - 7 Placebo -
- Primary Outcome Measures
Name Time Method 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) End of study visit (V4)
- Secondary Outcome Measures
Name Time Method Fasting blood insulin and fasting blood glucose, HbA1c. 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). End of study visit (V4) Insulin sensitivity assessed by the OGTT-derived composite whole-body Insulin Sensitivity Index (ISI) 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 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. End of study visit (V4) Body mass index (BMI), waist circumference, hip circumference, waist to hip ratio, and blood pressure. End of study visit (V4) Percentage of patients who presented 0, 1, 2, 3, 4 or 5 MetS criteria. End of study visit (V4) Adverse events (AEs). 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 End of study visit (V4) Hematology: white blood cells (WBC) and differential count, red blood cells (RBC), hemoglobin, hematocrit and platelets. End of study visit (V4) Blood pressure. End of study visit (V4)
Trial Locations
- Locations (101)
Site 007
🇨🇦Chicoutimi, Canada
Site 010
🇨🇦St. John's, Canada
Site 004
🇨🇦Hamilton, Canada
Site 003
🇨🇦Quebec, Canada
Site 024
🇨🇦Halifax, Canada
Site 077
🇮🇹Chieti Scalo, Italy
Site 012
🇨🇦Kingston, Canada
Site 090
🇫🇮Hus, Finland
Site 001
🇨🇦Montreal, Canada
Site 096
🇫🇮Narpes, Finland
Site 009
🇨🇦Montague, Canada
Site 017
🇨🇦Longueuil, Canada
Site 005
🇨🇦Vancouver, Canada
Site 016
🇨🇦Toronto, Canada
Site 192
🇭🇺Szekesfehervar, Hungary
Site 150
🇸🇪Linkoping, Sweden
Site 155
🇸🇪Lund, Sweden
Site 190
🇭🇺Budapest, Hungary
Site 197
🇭🇺Miskolc, Hungary
Site 196
🇭🇺Pecs, Hungary
Site 045
🇳🇱Groningen, Netherlands
Site 047
🇳🇱Rotterdam, Netherlands
Site 076
🇮🇹Padova, Italy
Site 072
🇮🇹Perugia, Italy
Site 070
🇮🇹Treviglio Bergamo, Italy
Site 006
🇨🇦Ste-Foy, Canada
Site 015
🇨🇦Montreal, Canada
Site 025
🇨🇦Sainte Foy, Canada
Site 026
🇨🇦Sainte Foy, Canada
Site 011
🇨🇦Victoria, Canada
Site 021
🇨🇦Sherbrooke, Canada
Site 022
🇨🇦St. John's, Canada
Site 020
🇨🇦St. John's, Canada
Site 191
🇭🇺Budapest, Hungary
Site 212
🇷🇴Bucharest, Romania
Site 205
🇭🇺Szombathely, Hungary
Site 195
🇭🇺Veszprem, Hungary
Site 074
🇮🇹Catanzaro, Italy
Site 075
🇮🇹Padova, Italy
Site 073
🇮🇹Palermo, Italy
Site 044
🇳🇱Almere, Netherlands
Site 046
🇳🇱Leiden, Netherlands
Site 057
🇳🇱Dordrecht, Netherlands
Site 055
🇳🇱Tiel, Netherlands
Site 053
🇳🇱Veldhoven, Netherlands
Site 117
🇳🇴Elverum, Norway
Site 112
🇳🇴Oslo, Norway
Site 132
🇵🇱Katowice, Poland
Site 131
🇵🇱Kielce, Poland
Site 133
🇵🇱Warsawa, Poland
Site 220
🇷🇴Brasov, Romania
Site 210
🇷🇴Bucharest, Romania
Site 214
🇷🇴Bucharest, Romania
Site 218
🇷🇴Bucharest, Romania
Site 219
🇷🇴Bucharest, Romania
Site 215
🇷🇴Cluj - Napoca, Romania
Site 217
🇷🇴Iasi, Romania
Site 153
🇸🇪Gothenburg, Sweden
Site 154
🇸🇪Kristianstad, Sweden
Site 152
🇸🇪Stockholm, Sweden
Site 213
🇷🇴Craiova, Romania
Site 216
🇷🇴Suceava, Romania
Site 151
🇸🇪Umea, Sweden
Site 201
🇭🇺Gyor, Hungary
Site 194
🇭🇺Szeged, Hungary
Site 211
🇷🇴Bucharest, Romania
Site 013
🇨🇦Calgary, Alberta, Canada
Site 200
🇭🇺Gyongyos, Hungary
Site 095
🇫🇮Jyvaskyla, Finland
Site 094
🇫🇮Vaasa, Finland
Site 054
🇳🇱Den Helder, Netherlands
Site 041
🇳🇱Hoorn, Netherlands
Site 043
🇳🇱Sliedrecht, Netherlands
Site 049
🇳🇱Zoetermeer, Netherlands
Site 060
🇳🇱Zwijndrecht, Netherlands
Site 199
🇭🇺Budapest, Hungary
Site 203
🇭🇺Debrecen, Hungary
Site 114
🇳🇴Hobol, Norway
Site 111
🇳🇴Horten, Norway
Site 113
🇳🇴Oslo, Norway
Site 139
🇵🇱Chrzanow, Poland
Site 135
🇵🇱Olsztyn, Poland
Site 193
🇭🇺Budapest, Hungary
Site 048
🇳🇱Velp, Netherlands
Site 056
🇳🇱Velp, Netherlands
Site 040
🇳🇱Amsterdam Zuidoost, Netherlands
Site 052
🇳🇱Groningen, Netherlands
Site 051
🇳🇱Rotterdam, Netherlands
Site 110
🇳🇴Oslo, Norway
Site 130
🇵🇱Brodnowski, Poland
Site 134
🇵🇱Gdansk, Poland
Site 204
🇭🇺Budapest, Hungary
Site 091
🇫🇮Jakobstad, Finland
Site 092
🇫🇮Mikkeli, Finland
Site 198
🇭🇺Gyula, Hungary
Site 042
🇳🇱Eindhoven, Netherlands
Site 019
🇨🇦Calgary, Alberta, Canada
Site 202
🇭🇺Budapest, Hungary
Site 138
🇵🇱Ul. Ziolowa, Poland
Site 118
🇳🇴Oslo, Norway
Site 115
🇳🇴Skedsmokorset, Norway