Study With GFT505 (80mg) Versus Placebo in Patients With Type 2 Diabetes Mellitus

• Oral Glucose Tolerance Test (OGTT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To evaluate the changes from baseline to end of treatment in OGTT parameters. Evaluation will be made prior the first treatment intake and 12 weeks after the first treatment intake.
• Fasting Plasma Glucose [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  To evaluate the changes from baseline to end of treatment in fasting plasma Glucose. Evaluation will be made during the selection period, prior any drug intake, and 4, 8, 12 weeks after the first treatment intake as well as 2 weeks after the last treatment intake (follow up period).
• Insulin resistance Index [fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR)] [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To evaluate the changes from baseline to end of treatment in insulin resistance index. Evaluation will be made during the selection period, prior any drug intake, and 4, 8, 12 weeks after the first treatment intake as well as 2 weeks after the last treatment intake (follow up period).

This study is expected to demonstrate the anti-diabetic efficacy of 3-months treatment with GFT505 (80 mg/d) on Glycosylated Haemoglobin A1c (HbA1C) and fasting plasma glucose.

And to assess the tolerability and safety of once-a-day administrations of oral doses of GFT505 for 12 weeks in patients with type 2 diabetes mellitus.

The study period per patient is 16-20 weeks maximum and is conducted as follows :

• Run-in period: 2 weeks or 6 weeks for patients under fibrate treatment at screening (4 weeks fibrate wash-out + 2 weeks placebo run-in);
• Treatment period: 12 weeks;
• Follow-up period: 2 weeks.

• Drug: GFT505 80mg
  hard gelatin capsules dosed at 20mg,oral administration,4 capsules per day before breakfast
• Drug: Placebo
  hard gelatin capsules,oral administration,4 capsules per day before breakfast

• Experimental: GFT505 80mg
  Intervention: Drug: GFT505 80mg
• Placebo Comparator: Matching placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Male or post-menopausal female (defined as >12 months since last menstrual period) or surgical menopause. If hormonal replacement therapy, it should be stable at least for 6 months prior to screening.
• Body Mass Index ≥27 and ≤45 kg/m².
• Drug-Naive patients with type 2 diabetes mellitus (non insulin dependent diabetes). Patients should not be treated by insulin or other diabetes medication for the last 3 months prior to screening. Patients treated for less than 4 weeks with insulin may be included in the study.
• HbA1c ≥ 7.0% and <9.5%.
• Antibody glutamate decarboxylase acid (Anti-GAD) negative for patients aged less than 40 years.

Exclusion Criteria:

• Type I Diabetes Mellitus.
• Blood Pressure > 160 / 95 mmHg.
• Lipid-lowering drugs such as fibrates.
• Fasting Plasma Glucose (FPG) ≥ 240 mg/dL.
• Triglycerides (TG) > 400 mg/dL.