Comparative Bioavailability - Gender Effect - Single and Multiple Ascending Dose Safety and Pharmacokinetic Study of GFT505

NCT01474161 | Completed Phase 1

• 2 other identifiers: GFT505-111-72011-004723-13
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor, Genfit, has developed a new formulation of GFT505 (60 mg). The objective is to compare the relative bioavailability between the new GFT505 formulation (capsule dosed at 60 mg GFT505) and the old GFT505 formulation (capsule dosed at 20 mg GFT505) in healthy male subjects and to assess the impact of gender on this relative bioavailability after administration in male and female subjects. Using the new formulation, a single and a multiple ascending dose study will be performed in overweight or obese male subjects otherwise healthy whose demographic and physiological characteristics are thought to be closer to those of the target population (Type 2 diabetes). Thereafter, a group of male and female patients with Type 2 diabetes will receive multiple dose administration of GFT505.

Conditions

Type 2 Diabetes; Diabetes Mellitus, Type 2; Metabolic Diseases; Cardiovascular Diseases; Obese; Dyslipidemia

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics parameters (Study Part I)

  For each subject at each Treatment Period, blood will be collected at the following time points: pre-dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 h post-dose.

  24h post-dose

• Safety parameters (Study Parts II, III and IV)

  Monitoring for the occurrence of AEs. Changes in physical examination, vital signs (blood pressure and pulse rate), ECG, and clinical laboratory tests (biochemistry, hematology, and urinalysis).

  Part II : 5 days ; Part III : 20 days ; Part IV : 20 days

Secondary Outcomes (2)

• Safety parameters (Study Part I)

  12 days for male and 5 days for female

• Pharmacokinetics parameters (Study Parts II, III and IV)

  Part II : 24h post-dose ; Part III : 15 days ; Part IV : 15 days

Study Arms (3)

Matching placebo

PLACEBO COMPARATOR

Drug: Placebo

GFT505 20mg - old formulation

ACTIVE COMPARATOR

Study Part I : dose level = 120mg

Drug: GFT505 120mg - old formulation

GFT505 60mg - new formulation

EXPERIMENTAL

Study Part I : dose level = 120mg ; Study Part II : dose level = 180mg, 240mg and 300mg ; Study Part III : dose level = 120mg, 180mg and 240mg ; Study Part IV : dose level = 120mg or 180mg.

Drug: GFT505 120mg - new formulation; Drug: GFT505 180mg - new formulation; Drug: GFT505 240mg - new formulation; Drug: GFT505 300mg - new formulation

Interventions

GFT505 120mg - old formulation DRUG

hard gelatin capsules dosed at 60mg, one single oral administration (Study part I), 6 capsules with 250mL of water.

GFT505 20mg - old formulation

GFT505 120mg - new formulation DRUG

hard gelatin capsules dosed at 60mg, one single oral administration (Study Part I) or multiple dose administration from Day 1 to Day 14 (Study Part III and IV), 2 capsules with 250mL of water.

GFT505 60mg - new formulation

GFT505 180mg - new formulation DRUG

hard gelatin capsules dosed at 60mg, one single oral administration (Study Part II) or multiple dose administration from Day 1 to Day 14 (Study Part III and IV), 3 capsules with 250mL of water.

GFT505 60mg - new formulation

GFT505 240mg - new formulation DRUG

hard gelatin capsules dosed at 60mg, one single oral administration (Study Part II) or multiple dose administration from Day 1 to Day 14 (Study Part III), 4 capsules with 250mL of water.

GFT505 60mg - new formulation

GFT505 300mg - new formulation DRUG

hard gelatin capsules dosed at 60mg, one single oral administration (Study Part II), 5 capsules with 250mL of water.

GFT505 60mg - new formulation

Placebo DRUG

hard gelatin capsules, one single oral administration (3 to 5 capsules with 250mL of water for Study Part II) or multiple dose administration from Day 1 to Day 14 (2 to 4 capsules with 250mL of water for Study Part III).

Matching placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part I :
• Male or female healthy volunteers 18 to 45 years of age (inclusive).
• Subjects with a body mass index (BMI) ≥ 18 and ≤ 28 kg/m2 at screening.
• For female subjects of childbearing potential, use of double contraception method.
• Normal arterial blood pressure (BP) and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator.
• Part II and III :
• Male healthy volunteers 18 to 55 years of age (inclusive).
• Subjects with a BMI \>28 and \<35 kg/m2 at screening.
• Normal arterial BP and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator.
• Part IV :
• Male or female Type 2 diabetic patients 18 to 60 years of age.
• Females participating in the study must be either of non-child bearing potential or using an efficient double contraception.
• Currently treated with any antidiabetic treatment (a maximum of two anti-diabetic drugs including metformin in all cases) with the exception of insulin or GLP analogs and agonists therapy.
• Stable diabetes with glycosylated hemoglobin (HbA1c) \< or =10% or less.
• Normal renal function as defined by a creatine clearance \>90 mL/min calculated with the Cockcroft-Gault formula.

You may not qualify if:

• Part I :
• Who previously received GFT505.
• With any clinically significant abnormality following review of prestudy laboratory tests (Aspartate and Alanine aminotransferase must be within normal ranges), vital signs, full physical examination and Electrocardiogram.
• Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 (Human immunodeficiency virus) or anti-HCV (Hepatitis C virus) antibodies.
• Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol).
• Who drink more than 8 cups daily of beverage containing caffeine.
• Who have a positive laboratory test for urine drug screening (opiates, cocaine, amphetamine, cannabis, benzodiazepines).
• Who have undergone surgery or have donated blood within 12 weeks prior to the start of the study.
• Who have taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the first dose administration.
• \- Who have taken fibrates within 6 weeks prior to the first dose administration.
• With unstable proliferative retinopathy, macular oedema (fundus examination performed in the previous year will be considered relevant on Investigator's judgement).
• Who have taken fibrates within 6 weeks prior to the first dose administration.

Sponsors & Collaborators

• Genfit: lead
• SGS Aster S.A.S.: collaborator
• Naturalpha: collaborator

Study Sites (1)

SGS Aster S.A.S. - Phase I Clinical Unit

Paris, 75015, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Metabolic Diseases; Cardiovascular Diseases; Obesity; Dyslipidemias

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lipid Metabolism Disorders

Study Officials

• Rémy Hanf, Development Director

  GENFIT, France

  STUDY DIRECTOR

• Philippe Betting, MD

  SGS Aster S.A.S., Phase I Clinical Unit, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: November 18, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 27, 2012

Record last verified: 2012-11

Locations

FR (1)