Elafibranor Pharmacokinetic Parameters in Elderly Healthy Volunteers

NCT04171752 | Completed Phase 1

• 2 other identifiers: GFT505-119-162019-001819-23
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

In the elderly, pharmacokinetics is altered. Gastric juice pH is elevated which influences drug solubility and absorption. Drug distribution is decreased in the elderly because of decreased cardiac output, increased peripheral vascular resistance, diminished blood flow in the liver and the kidneys, reduced total amount of water in the body. Drug metabolism and biotransformation mainly take place in the liver and is often reduced. Drug elimination is altered very often because of reduced excretory (renal and hepatic) function. All these changes may lead to significant pharmacokinetic changes in geriatric population. A formal pharmacokinetic clinical study is being conducted in order to assess the need of dose adjustment in the elderly population.

Conditions

Geriatrics; Healthy

Keywords

elafibranor

Outcome Measures

Primary Outcomes (3)

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

  In Healthy Young Adults compared to Healthy Elderly

  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 elderly volunteers

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

  In Healthy Young Adults compared to Healthy Elderly

  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 elderly volunteers

• Plasma pharmacokinetics: maximum plasma drug concentration (Cmax) of elafibranor and active metabolite

  In Healthy Young Adults compared to Healthy Elderly

  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 elderly volunteers

Secondary Outcomes (14)

• 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 elderly volunteers

• Plasma pharmacokinetics: area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total area under the plasma

  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 elderly volunteers

• Plasma pharmacokinetics: time of maximum observed concentration (tmax)

  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 elderly volunteers

• 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 elderly volunteers

• Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞))

  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 elderly volunteers

Study Arms (2)

Young Adults

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: elafibranor

Elderly

EXPERIMENTAL

Single oral dose of elafibranor 120mg

Drug: elafibranor

Interventions

elafibranor DRUG

elafibranor 120mg is a coated tablet for oral administration

Also known as: GFT505

Elderly; Young Adults

Eligibility Criteria

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

You may qualify if:

• \- For All Participants:
• Provide written informed consent prior to the conduct of any study related procedures;
• With a minimum body weight (BW) of 50 kg and within a Body Mass Index (BMI) range of 18.0 to 30.0 kg/m\^2 (all inclusive) at Screening visit;
• Absence of clinically relevant abnormalities identified by a detailed medical history and complete physical examination;
• Laboratory parameters within the normal range of the laboratory;
• Able to comprehend and willing to sign an Informed Consent Form, and to abide by the study restrictions;
• Participant with normal dietary habits;
• Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research;
• For Healthy Young Volunteers only:
• Males or females, between 18 and 45 years of age (all inclusive) at screening;
• Matched to healthy elderly participants by BMI (plus or minus 20 percent) and gender;
• Females participating in this study must be of non-childbearing potential or using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment;
• For Elderly volunteers only:
• Males or females aged 75 years old or older at Screening visit;
• Participants with mild, chronic, stable disease and stable treatment dose - no change in dose for the 3 months prior to Screening visit - (hypertension, hyperlipidemia, osteoarthritis, treated benign prostate hypertrophy, stable and treated hypothyroidism, treated glaucoma);

You may not qualify if:

• \- For all participants:
• Participants with a history of noncompliance to medical regimens;
• Participant who, in the opinion of the Investigator, is likely to be not respectful or not cooperative during the study, or unable to cooperate because of a language problem or a mental deficiency;
• Participant who cannot be contacted in case of emergency;
• Administrative or legal supervision;
• Inability to abstain from intensive muscular effort;
• Participant who would receive more than 4500 euros as indemnities for his participation in biomedical research within the 12 last months, including the indemnities for the present study;
• Any history or suspicion of alcohol abuse;
• Any history or suspicion of consumption of any drug of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methamphetamines, methadone, methylenedioxymethamphetamine, opiates, tricyclic antidepressant), from screening to end of the study;
• Consumption of nutritional supplements, herb-containing drug preparations (including Chinese medicines) or other foods or beverages (e.g., grapefruit and xanthine-containing foods or beverages) that may affect drug-metabolizing enzymes or transporters from screening to end of the study visit;
• Evidence or history of gastrointestinal, hepatic, or renal disease, surgery or resection that would potentially alter absorption, distribution, metabolism, or excretion of orally administered drugs;
• Participants who have clinically significant disease of cardiovascular, respiratory, renal, endocrine, hematological, gastrointestinal, neurological (central nervous system), psychiatric, systemic, infectious disorders or malignant tumor;
• General anesthesia within 3 months before administration;
• History or presence of allergy or unusual reactions to some drugs or anesthetics or known hypersensibility to the investigation product or its excipients;
• Major surgery within 28 days prior to Screening visit or major surgery planned within 6 months following participation to the study;

Sponsors & Collaborators

• Genfit: lead

Study Sites (1)

BIOTRIAL

Rennes, 35042, France

Location

MeSH Terms

Interventions

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

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

Model Details: Open-label, non-randomized, single-center, single-dose, two arms Phase 1 study in healthy elderly, aged of at least 75 years old (inclusive) and in healthy young adults, aged between 18 and 45 years old (all inclusive)

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 21, 2019
• Study Start: November 22, 2019
• Primary Completion: March 22, 2020
• Study Completion: March 30, 2020
• Last Updated: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)