Elafibranor Pharmacokinetic Parameters in Hepatic Impaired Patients

NCT03765671 | Completed Phase 1 FDA Drug

• 1 other identifier: GFT505-118-14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being conducted in order to assess the need for dose adjustment for elafibranor in patients with hepatic impairment. Pharmacokinetic parameters of elafibranor and its active metabolite (GFT1007) will be compared in hepatic impaired patients (mild, moderate and severe according to Child-Pugh categories) versus healthy participants after a single oral administration of elafibranor 120 mg.

Conditions

Hepatic Impairment; Liver Disease; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Area under curve from dosing time to last measurement (AUC(0-t)) of elafibranor and active metabolite

  In participants with mild, moderate and severe hepatic impairment compared to healthy volunteers

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired patients

• Area under curve from dosing time to infinity (AUC(0-∞)) of elafibranor and active metabolite

  In participants with mild, moderate and severe hepatic impairment compared to healthy volunteers

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired patients

Secondary Outcomes (14)

• Plasma pharmacokinetics: maximum plasma drug concentration (Cmax)

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants

• Plasma pharmacokinetics: elimination half-life (t1/2)

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants

• Plasma pharmacokinetics: apparent volume of distribution (Vd/F)

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants

• Plasma pharmacokinetics: renal clearance (CLr)

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants

• Plasma pharmacokinetics: apparent non renal clearance (CLnr/F)

  pre-dose and at 0.17, 0.33, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192 and 216 hours post-dose. Additionally, after elafibranor administration at 288 and 384 hours for hepatic impaired participants

Study Arms (4)

Mild Child-Pugh A

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: Elafibranor

Moderate Child-Pugh B

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: Elafibranor

Severe Child-Pugh C

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: Elafibranor

Healthy

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: Elafibranor

Interventions

Elafibranor DRUG

120mg oral single dose

Also known as: GFT505

Healthy; Mild Child-Pugh A; Moderate Child-Pugh B; Severe Child-Pugh C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- For all participants:
• Males or females, between 18 and 75 years of age, inclusive;
• With a minimum body weight of 50 kg and within a BMI range of 18.0 to 40.0 kg/m², inclusive;
• Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study
• Negative serum pregnancy test at screening (if applicable);
• Negative human immunodeficiency virus antibody screens at Screening;
• For hepatically impaired participants:
• Participants who have chronic (≥ 6 months) mild, moderate, or severe hepatic insufficiency (of any etiology) that has been clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to Screening Currently on a stable medication regimen
• For healthy volunteers with normal hepatic function:
• Non-smokers
• Matched to participants with Mild and/or Moderate and/or Severe hepatic impairment in age (± 10 years), BMI (± 20 percent) and gender.

You may not qualify if:

• \- For all participants:
• A positive alcohol test result at Check-in;
• A history of alcohol abuse in the prior 2 years;
• Positive urine screen for drugs of abuse at Screening or Check-in.
• Strenuous exercise within 72 hours prior to Check-in;
• Blood donation or loss of blood (excluding volume drawn at screening or menses) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the dosing;
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs except that appendectomy and hernia repair will be allowed. Bariatric surgery will not be allowed.
• Presence or history of malignancy within the prior 3 years, with the exception of treated basal cell or squamous cell carcinoma;
• Poor peripheral venous access;
• Receipt of blood products within 2 months prior to Check-in;
• For hepatically impaired participants:
• History of unstable diabetes mellitus Subjects who have a transjugular intrahepatic portosystemic shunt and/or have undergone portacaval shunting;
• Participant has shown evidence of hepatorenal syndrome or has creatinine clearance ≤ 60 mL/min Subject has required treatment for GI bleeding within the 6 months prior to Check in;
• Recent history of paracentesis (\< 3 months prior to Check-in);
• Participants with Wilson's disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, or galactosemia;

Sponsors & Collaborators

• Genfit: lead
• Syneos Health: collaborator
• University of Miami: collaborator

Study Sites (2)

Division of Clinical Pharmacology, University of Miami

Miami, Florida, 33136, United States

Location

inVentiv Health Clinical Research

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

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

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Pascal BIRMAN, MD

  Genfit

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 5, 2018
• Study Start: December 12, 2018
• Primary Completion: June 7, 2019
• Study Completion: June 14, 2019
• Last Updated: August 22, 2019

Record last verified: 2019-08

Locations

US (2)