Elafibranor Pharmacokinetic Parameters in Renal Impaired Patients

NCT03844555 | Completed Phase 1

• 2 other identifiers: GFT505-118-132018-002481-39
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is being conducted in order to assess the need for dose adjustment for elafibranor in participants with renal impairment. Pharmacokinetic parameters of elafibranor and its active metabolite (GFT1007) will be compared in severe renal impaired participants (eGFR\<15mL/mn/1.73m\^2) versus healthy participants after a single oral administration of elafibranor 120 mg

Conditions

Renal Impairment; Renal Insufficiency; Kidney Diseases; 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 end stage renal disease 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

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

  In participants with end stage renal disease 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

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

• 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

• 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

• 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

• 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

Study Arms (2)

End Stage Renal Disease

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

End Stage Renal Disease; Healthy

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
• Male or female subjects, aged 18 to 75 years 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);
• Non-smoker subject or smoker of not more than 5 cigarettes a day;
• For Renally Impaired Participants
• ESRD patient not yet on dialysis with an estimated glomerular filtration rate (eGFR) \<15mL/min/1.73m\^2;
• Documented renal impairment indicated by reduced eGFR within 12 months of screening or longer;
• Stable renal function as evidenced by ≤ 30 percent difference in two evaluation of eGFR on two separate occasions separated by at least 28 days with one measurement being the value at screening;
• Body Mass Index (BMI) between 20 and 36 kg/m\^2 inclusive.
• For Healthy Volunteers with normal renal function:
• eGFR ≥ 90mL/min/1.73m\^2;
• No proteinuria (\< 0.15 g/L determined by urinalysis);
• Body Mass Index between 20 and 30 kg/m\^2 inclusive and body weight not lower than 55kg;
• Matched to at least 1 renal impaired patient by ethnic group, sex, age (+/- 10 years) and BMI (+/- 20 percent).

You may not qualify if:

• All Participants
• Positive Hepatitis B surface antigen or anti Hepatitis C Virus antibody, or positive results for Human Immunodeficiency Virus 1 or 2 tests;
• History or presence of drug or alcohol abuse (alcohol consumption \> 40 grams/day);
• Blood donation (including in the frame of a clinical trial) within 2 months before administration or blood donation planned during the study or within 2 months following participation to the study;
• Participants who are pregnant or breastfeeding. Participants should not be enrolled if they plan to become pregnant during the time of study participation;
• Positive results of screening for drugs of abuse;
• Evidence or history of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic, systemic, infectious, or allergic disease (including drug hypersensitivity or allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing);
• General anesthesia within 3 months before administration;
• Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
• For Renally Impaired Participants:
• History of renal transplant;
• Evidence of an unstable clinically important medical condition other than impaired renal function;
• Acute exacerbation or unstable renal function, as indicated by worsening of clinical and/or laboratory signs of renal impairment, within the 4 weeks before study drug administration;
• Participants undergoing any method of dialysis or hemofiltration;
• Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the pharmacokinetics of the investigational medicinal product (e.g., inflammatory bowel disease, resections of the small or large intestine, etc.);

Sponsors & Collaborators

• Genfit: lead

Study Sites (2)

Eurofins Optimed

Gières, 38610, France

Location

ARENSIA Exploratory Medicine Unit, Nephrology Hospital Dr. Carol Davilla

Bucharest, 010701, Romania

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases

Interventions

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

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital 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: February 15, 2019
• First Posted: February 18, 2019
• Study Start: February 28, 2019
• Primary Completion: March 15, 2020
• Study Completion: March 21, 2020
• Last Updated: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1); FR (1)