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

Sponsor

Solvay Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00703755

Collaborator

(none)

2,288

Enrollment

101

Locations

Arms

Duration (Months)

22.7

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

2288 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, 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.

Study Start Date :

Mar 1, 2003

Actual Primary Completion Date :

Jun 1, 2004

Actual Study Completion Date :

Jun 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

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) [End of study visit (V4)]

Secondary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country
1	Site 013	Calgary	Alberta	Canada
2	Site 019	Calgary	Alberta	Canada
3	Site 007	Chicoutimi		Canada
4	Site 024	Halifax		Canada
5	Site 004	Hamilton		Canada
6	Site 012	Kingston		Canada
7	Site 017	Longueuil		Canada
8	Site 009	Montague		Canada
9	Site 001	Montreal		Canada
10	Site 015	Montreal		Canada
11	Site 003	Quebec		Canada
12	Site 025	Sainte Foy		Canada
13	Site 026	Sainte Foy		Canada
14	Site 021	Sherbrooke		Canada
15	Site 010	St. John's		Canada
16	Site 020	St. John's		Canada
17	Site 022	St. John's		Canada
18	Site 006	Ste-Foy		Canada
19	Site 016	Toronto		Canada
20	Site 005	Vancouver		Canada
21	Site 011	Victoria		Canada
22	Site 090	Hus		Finland
23	Site 091	Jakobstad		Finland
24	Site 095	Jyvaskyla		Finland
25	Site 092	Mikkeli		Finland
26	Site 096	Narpes		Finland
27	Site 094	Vaasa		Finland
28	Site 190	Budapest		Hungary
29	Site 191	Budapest		Hungary
30	Site 193	Budapest		Hungary
31	Site 199	Budapest		Hungary
32	Site 202	Budapest		Hungary
33	Site 204	Budapest		Hungary
34	Site 203	Debrecen		Hungary
35	Site 200	Gyongyos		Hungary
36	Site 201	Gyor		Hungary
37	Site 198	Gyula		Hungary
38	Site 197	Miskolc		Hungary
39	Site 196	Pecs		Hungary
40	Site 194	Szeged		Hungary
41	Site 192	Szekesfehervar		Hungary
42	Site 205	Szombathely		Hungary
43	Site 195	Veszprem		Hungary
44	Site 074	Catanzaro		Italy
45	Site 077	Chieti Scalo		Italy
46	Site 075	Padova		Italy
47	Site 076	Padova		Italy
48	Site 073	Palermo		Italy
49	Site 072	Perugia		Italy
50	Site 070	Treviglio Bergamo		Italy
51	Site 044	Almere		Netherlands
52	Site 040	Amsterdam Zuidoost		Netherlands
53	Site 054	Den Helder		Netherlands
54	Site 057	Dordrecht		Netherlands
55	Site 042	Eindhoven		Netherlands
56	Site 045	Groningen		Netherlands
57	Site 052	Groningen		Netherlands
58	Site 041	Hoorn		Netherlands
59	Site 046	Leiden		Netherlands
60	Site 047	Rotterdam		Netherlands
61	Site 051	Rotterdam		Netherlands
62	Site 043	Sliedrecht		Netherlands
63	Site 055	Tiel		Netherlands
64	Site 053	Veldhoven		Netherlands
65	Site 048	Velp		Netherlands
66	Site 056	Velp		Netherlands
67	Site 049	Zoetermeer		Netherlands
68	Site 060	Zwijndrecht		Netherlands
69	Site 117	Elverum		Norway
70	Site 114	Hobol		Norway
71	Site 111	Horten		Norway
72	Site 110	Oslo		Norway
73	Site 112	Oslo		Norway
74	Site 113	Oslo		Norway
75	Site 118	Oslo		Norway
76	Site 115	Skedsmokorset		Norway
77	Site 130	Brodnowski		Poland
78	Site 139	Chrzanow		Poland
79	Site 134	Gdansk		Poland
80	Site 132	Katowice		Poland
81	Site 131	Kielce		Poland
82	Site 135	Olsztyn		Poland
83	Site 138	Ul. Ziolowa		Poland
84	Site 133	Warsawa		Poland
85	Site 220	Brasov		Romania
86	Site 210	Bucharest		Romania
87	Site 211	Bucharest		Romania
88	Site 212	Bucharest		Romania
89	Site 214	Bucharest		Romania
90	Site 218	Bucharest		Romania
91	Site 219	Bucharest		Romania
92	Site 215	Cluj - Napoca		Romania
93	Site 213	Craiova		Romania
94	Site 217	Iasi		Romania
95	Site 216	Suceava		Romania
96	Site 153	Gothenburg		Sweden
97	Site 154	Kristianstad		Sweden
98	Site 150	Linkoping		Sweden
99	Site 155	Lund		Sweden
100	Site 152	Stockholm		Sweden
101	Site 151	Umea		Sweden