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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Comparative Bioavailability Study of a New GFT505 Formulation With the Existing One After 120 mg Single Oral GFT505 Administration and Assessment of the Gender Effect in Young Healthy Male and Female Volunteers Followed by a Single and Multiple Ascending Dose Safety, Tolerability and Pharmacokinetic Study of GFT505 in Overweight or Obese Subjects and in Diabetic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01474161
• Other study ID #: GFT505-111-7
• Secondary ID: 2011-004723-13
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2011
• Last updated: November 23, 2012
• Start date: November 2011
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Genfit
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Description:

The study will be divided in 4 successive parts :

• Study Part I will be a comparative bioavailability between a new GFT505 formulation (capsule dosed at 60 mg GFT505 by capsule) and the old GFT505 formulation (capsule dosed at 20 mg GFT505 by capsule) coupled with an evaluation of the gender effect assessed with the new formulation. In this purpose a group of 12 male subjects will receive successively both formulations on a unique occasion in a randomized manner while a group of 12 female subjects will receive the new formulation on one occasion only. This part of the study will be done in healthy volunteers.

• Study Part II will be a single ascending dose to be run at a maximum of 3 dose levels. Subjects included in this part of the study will receive only one dose level to limit the exposure to GFT505. Three cohorts of 8 subjects are planned to be included. This part will be run in overweight or obese subjects.

• Study Part III will start after completion of the first Cohort of Study Part II. Study Part III will be a multiple ascending dose to be run at a maximum of 3 dose levels. Subjects included in this part of the study will receive only one dose level to limit the exposure to GFT505. Three cohorts of 12 subjects are planned to be included. This part will be run in overweight or obese subjects.

• Study Part IV will follow the same design and same treatment schedule than Study Part III but will be performed in the target population, patients with Type 2 diabetes and only one dose will be tested in study part IV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

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.

• Subjects with a BMI from 18 to 32 kg/m2 at screening.

Exclusion Criteria:

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.

Part II and III : specific additional exclusion criteria

• Who have taken fibrates within 6 weeks prior to the first dose administration.

Part IV : specific additional exclusion criteria

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Dyslipidemia
• Dyslipidemias
• Metabolic Diseases
• Obese
• Type 2 Diabetes

Intervention

Drug:
• GFT505 120mg - old formulation
hard gelatin capsules dosed at 60mg, one single oral administration (Study part I), 6 capsules with 250mL of water.
• GFT505 120mg - new formulation
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 180mg - new formulation
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 240mg - new formulation
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 300mg - new formulation
hard gelatin capsules dosed at 60mg, one single oral administration (Study Part II), 5 capsules with 250mL of water.
• Placebo
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).

Locations

Country	Name	City	State
France	SGS Aster S.A.S. - Phase I Clinical Unit	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Genfit	Naturalpha, SGS Aster S.A.S.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes
Secondary	Safety parameters (Study Part I)	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).	12 days for male and 5 days for female	Yes
Secondary	Pharmacokinetics parameters (Study Parts II, III and IV)	Study Part II : For each subject of each dose level, 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.; Study Part III and Study Part IV : Assuming a once daily administration, blood will be collected at the following time points: Day 1 pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 h post-dose.; Days 3, 7, 10, 11, 12 and 13 pre-dose.; Day 14 pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 h post-dose.	Part II : 24h post-dose ; Part III : 15 days ; Part IV : 15 days	No