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

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.

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Abdominal Obesity
• Intervention / Treatment: Drug: GFT505 80mg; Drug: Placebo

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nantes Cedex 1, France, 44093
    • Site n°1
  • Pierre Bénite, France, 69310
    • Site n°2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genfit
• Investigators: Study Chair: Bertrand CARIOU, Pr., University Hospital of Nantes, France

Publications and helpful links

General Publications

• Cariou B, Hanf R, Lambert-Porcheron S, Zair Y, Sauvinet V, Noel B, Flet L, Vidal H, Staels B, Laville M. Dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. Diabetes Care. 2013 Oct;36(10):2923-30. doi: 10.2337/dc12-2012. Epub 2013 May 28.
• Staels B, Rubenstrunk A, Noel B, Rigou G, Delataille P, Millatt LJ, Baron M, Lucas A, Tailleux A, Hum DW, Ratziu V, Cariou B, Hanf R. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology. 2013 Dec;58(6):1941-52. doi: 10.1002/hep.26461. Epub 2013 Oct 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: January 4, 2011
• First Submitted That Met QC Criteria: January 6, 2011
• First Posted (Estimate): January 7, 2011

Study Record Updates

• Last Update Posted (Estimate): September 24, 2012
• Last Update Submitted That Met QC Criteria: September 21, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Insulin resistance; Pre-diabetes; PPARs; Clamp technique
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Insulin Resistance; Obesity, Abdominal
• Other Study ID Numbers: GFT505-210-6; 2010-023219-32 (EudraCT Number)