Pilot Study With GFT505 (80mg) in Patients With Insulin Resistance and Abdominal Obesity

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy on insulin sensitivity of GFT505 at 80mg/d in male patients with insulin resistance and abdominal obesity. Evaluation will be made using a glucose clamp technique.

Detailed Description
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The study period per patient is 26 weeks: a selection period will precede a 8-week treatment period, a 6-week wash out period, a second 8-week treatment period in the second arm of treatment and a 2- week follow-up period. Schedule: Selection visit prior to treatment period (D-14 and D-1) D0 : randomisation visit Period T1: first period of treatment with GFT505 80mg or placebo for 8 weeks (D1 to D56) Wash out period for 6 weeks (D57 to D98) Period T2: second period of treatment with GFT505 80mg or placebo for 8 weeks (D99 to D154) Follow up period for 2 weeks (D155 to D169)

Official Title
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A Pilot Study to Evaluate the Efficacy of GFT505 (80mg) Orally Administered Once Daily for 8 Weeks on Insulin Sensitivity Using a Glucose Clamp Technique and Safety in Male Patients With Insulin Resistance and Abdominal Obesity. A Multicentre, Randomised, Single Blind, Placebo-Controlled, Cross Over Study.

Conditions
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Insulin Resistance, Abdominal Obesity

Intervention / Treatment
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* Drug: GFT505 80mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Waist circumference ≥94cm. Body Mass Index ≤ 45kg/m2. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) > 3. Exclusion Criteria: Blood Pressure > 160 / 95 mmHg. Diabetes mellitus 1 or 2. Historical of bariatric surgery. Patient treated with a lipid-decreasing medication. A fasting plasma triglycerides concentration > 400mg/dL or a plasma Low Density Lipoprotein Cholesterol (LDL-c)concentration > 220mg/dL.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GFT505 80mg<br> | Drug: GFT505 80mg<br>* hard gelatin capsules dosed at 20mg, oral administration, 4 capsules per day before breakfast<br>|
| Placebo Comparator: Matching placebo<br> | Drug: Placebo<br>* hard gelatin capsules, oral administration, 4 capsules per day before breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Infusion Rate (GIR) | To evaluate in each patient the differences in Glucose Infusion Rate (GIR) measured at the end of 8 weeks treatment periods with GFT505 (80 mg/day per os) or placebo according to a cross-over design. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Hepatic Glucose Production (HGP) in each patient | To evaluate in each patient the differences in Hepatic Glucose Production (HGP) measured at the end of 8 weeks treatment periods with GFT505 (80 mg/day per os) or placebo according to a cross-over design. | 8 weeks | 
| Changes in GIR (Glucose Infusion Rate) | To compare the changes from baseline to endpoint in Glucose Infusion Rate (GIR). The baseline will be defined as the values of glucose clamp at V2. The same baseline will be used for the 2 periods. End-points will be defined as glucose clamp values at V4 for the first period and as glucose clamp values at V7 for the second period. | 8 weeks | 
| Changes in HGP (Hepatic Glucose Production) | To compare the changes from baseline to endpoint in Hepatic Glucose Production (HGP). The baseline will be defined as the values of glucose clamp at V2. The same baseline will be used for the 2 periods. End-points will be defined as glucose clamp values at V4 for the first period and as glucose clamp values at V7 for the second period. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-diabetes, Clamp technique, PPARs, Insulin resistance