Clinical trial NCT00703755: A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.
Official title: A Randomized, Double-Blind Trial Comparing the Efficacy and Safety of Fenofibrate, Metformin, Their Combination and Placebo in Patients With Metabolic Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Patients With Metabolic Syndrome
Keywords: Diabetes
Hypertriglyceridaemia
Metabolic Syndrome
Lead sponsor: Solvay Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-06-23
Enrollment: 2288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: End of study visit (V4)
Secondary outcomes:
measure: Fasting blood insulin and fasting blood glucose, HbA1c.
timeFrame: End of study visit (V4)
measure: 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).
timeFrame: End of study visit (V4)
measure: Insulin sensitivity assessed by the OGTT-derived composite whole-body Insulin Sensitivity Index (ISI)
timeFrame: End of study visit (V4)
measure: 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
timeFrame: End of study visit (V4)
measure: 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.
timeFrame: End of study visit (V4)
measure: Body mass index (BMI), waist circumference, hip circumference, waist to hip ratio, and blood pressure.
timeFrame: End of study visit (V4)
measure: Percentage of patients who presented 0, 1, 2, 3, 4 or 5 MetS criteria.
timeFrame: End of study visit (V4)
measure: Adverse events (AEs).
timeFrame: End of study visit (V4)
measure: Biochemistry: creatinine phosphokinase (CPK), AST, ALT, GGT, alkaline phosphatase, serum creatinine, total bilirubin, blood urea nitrogen (BUN), uric acid, albumin and total homocysteine
timeFrame: End of study visit (V4)
measure: Hematology: white blood cells (WBC) and differential count, red blood cells (RBC), hemoglobin, hematocrit and platelets.
timeFrame: End of study visit (V4)
measure: Blood pressure.
timeFrame: End of study visit (V4)
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Site 013
state: Alberta
city: Calgary
country: Canada
facility: Site 019
state: Alberta
city: Chicoutimi
country: Canada
facility: Site 007
city: Halifax
country: Canada
facility: Site 024
city: Hamilton
country: Canada
facility: Site 004
city: Kingston
country: Canada
facility: Site 012
city: Longueuil
country: Canada
facility: Site 017
city: Montague
country: Canada
facility: Site 009
city: Montreal
country: Canada
facility: Site 001
city: Montreal
country: Canada
facility: Site 015
city: Quebec
country: Canada
facility: Site 003
city: Sainte Foy
country: Canada
facility: Site 025
city: Sainte Foy
country: Canada
facility: Site 026
city: Sherbrooke
country: Canada
facility: Site 021
city: St. John's
country: Canada
facility: Site 010
city: St. John's
country: Canada
facility: Site 020
city: St. John's
country: Canada
facility: Site 022
city: Ste-Foy
country: Canada
facility: Site 006
city: Toronto
country: Canada
facility: Site 016
city: Vancouver
country: Canada
facility: Site 005
city: Victoria
country: Canada
facility: Site 011
city: Hus
country: Finland
facility: Site 090
city: Jakobstad
country: Finland
facility: Site 091
city: Jyvaskyla
country: Finland
facility: Site 095
city: Mikkeli
country: Finland
facility: Site 092
city: Narpes
country: Finland
facility: Site 096
city: Vaasa
country: Finland
facility: Site 094
city: Budapest
country: Hungary
facility: Site 190
city: Budapest
country: Hungary
facility: Site 191
city: Budapest
country: Hungary
facility: Site 193
city: Budapest
country: Hungary
facility: Site 199
city: Budapest
country: Hungary
facility: Site 202
city: Budapest
country: Hungary
facility: Site 204
city: Debrecen
country: Hungary
facility: Site 203
city: Gyongyos
country: Hungary
facility: Site 200
city: Gyor
country: Hungary
facility: Site 201
city: Gyula
country: Hungary
facility: Site 198
city: Miskolc
country: Hungary
facility: Site 197
city: Pecs
country: Hungary
facility: Site 196
city: Szeged
country: Hungary
facility: Site 194
city: Szekesfehervar
country: Hungary
facility: Site 192
city: Szombathely
country: Hungary
facility: Site 205
city: Veszprem
country: Hungary
facility: Site 195
city: Catanzaro
country: Italy
facility: Site 074
city: Chieti Scalo
country: Italy
facility: Site 077
city: Padova
country: Italy
facility: Site 075
city: Padova
country: Italy
facility: Site 076
city: Palermo
country: Italy
facility: Site 073
city: Perugia
country: Italy
facility: Site 072
city: Treviglio Bergamo
country: Italy
facility: Site 070
city: Almere
country: Netherlands
facility: Site 044
city: Amsterdam Zuidoost
country: Netherlands
facility: Site 040
city: Den Helder
country: Netherlands
facility: Site 054
city: Dordrecht
country: Netherlands
facility: Site 057
city: Eindhoven
country: Netherlands
facility: Site 042
city: Groningen
country: Netherlands
facility: Site 045
city: Groningen
country: Netherlands
facility: Site 052
city: Hoorn
country: Netherlands
facility: Site 041
city: Leiden
country: Netherlands
facility: Site 046
city: Rotterdam
country: Netherlands
facility: Site 047
city: Rotterdam
country: Netherlands
facility: Site 051
city: Sliedrecht
country: Netherlands
facility: Site 043
city: Tiel
country: Netherlands
facility: Site 055
city: Veldhoven
country: Netherlands
facility: Site 053
city: Velp
country: Netherlands
facility: Site 048
city: Velp
country: Netherlands
facility: Site 056
city: Zoetermeer
country: Netherlands
facility: Site 049
city: Zwijndrecht
country: Netherlands
facility: Site 060
city: Elverum
country: Norway
facility: Site 117
city: Hobol
country: Norway
facility: Site 114
city: Horten
country: Norway
facility: Site 111
city: Oslo
country: Norway
facility: Site 110
city: Oslo
country: Norway
facility: Site 112
city: Oslo
country: Norway
facility: Site 113
city: Oslo
country: Norway
facility: Site 118
city: Skedsmokorset
country: Norway
facility: Site 115
city: Brodnowski
country: Poland
facility: Site 130
city: Chrzanow
country: Poland
facility: Site 139
city: Gdansk
country: Poland
facility: Site 134
city: Katowice
country: Poland
facility: Site 132
city: Kielce
country: Poland
facility: Site 131
city: Olsztyn
country: Poland
facility: Site 135
city: Ul. Ziolowa
country: Poland
facility: Site 138
city: Warsawa
country: Poland
facility: Site 133
city: Brasov
country: Romania
facility: Site 220
city: Bucharest
country: Romania
facility: Site 210
city: Bucharest
country: Romania
facility: Site 211
city: Bucharest
country: Romania
facility: Site 212
city: Bucharest
country: Romania
facility: Site 214
city: Bucharest
country: Romania
facility: Site 218
city: Bucharest
country: Romania
facility: Site 219
city: Cluj - Napoca
country: Romania
facility: Site 215
city: Craiova
country: Romania
facility: Site 213
city: Iasi
country: Romania
facility: Site 217
city: Suceava
country: Romania
facility: Site 216
city: Gothenburg
country: Sweden
facility: Site 153
city: Kristianstad
country: Sweden
facility: Site 154
city: Linkoping
country: Sweden
facility: Site 150
city: Lund
country: Sweden
facility: Site 155
city: Stockholm
country: Sweden
facility: Site 152
city: Umea
country: Sweden
facility: Site 151
Study officials:
affiliation: Solvay Pharmaceuticals
name: Global Clinical Director Solvay
role: STUDY_DIRECTOR
References: