Study to Investigate the Potential Drug-Drug Interaction Between Elafibranor and Indomethacin

NCT03985969 | Completed Phase 1

• 2 other identifiers: GFT505-119-152019-001451-38
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The enzyme responsible for the conversion of elafibranor into its active metabolite, GFT1007, has not been formally identified, but it is believed to have similar characteristics to an α,β-ketoalkene reductase previously identified in rat liver cytosol. In vitro studies in human liver cytosol fractions have shown that indomethacin inhibits the enzyme responsible of the transformation of elafibranor into GFT1007. As a result, indomethacin was included in the list of prohibited co-medications in all clinical trials with elafibranor, and a formal Drug-Drug Interaction (DDI) clinical study is being conducted to elucidate the effect of indomethacin on elafibranor pharmacokinetics.

Conditions

Drug-drug Interaction

Keywords

Healthy volunteers; Elafibranor

Outcome Measures

Primary Outcomes (2)

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

  of elafibranor

  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 (336 and 384 hours post-dose added in sequence 2)

• Plasma pharmacokinetics: Maximum plasma drug concentration (Cmax)

  of elafibranor

  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 (336 and 384 hours post-dose added in sequence 2)

Secondary Outcomes (2)

• 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 (336 and 384 hours post-dose added in sequence 2)

• 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 (336 and 384 hours post-dose added in sequence 2)

Other Outcomes (6)

• Plasma pharmacokinetics: Area under curve from dosing time to last measurement (AUC(0-t))

  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 (336 and 384 hours post-dose added in sequence 2)

• 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 (336 and 384 hours post-dose added in sequence 2)

• 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 (336 and 384 hours post-dose added in sequence 2)

Study Arms (1)

DDI

EXPERIMENTAL

Period 1: study of elafibranor's pharmacokinetics Period 2: study of elafibranor's pharmacokinetics under CHRONO-INDOCID® (indomethacin) at steady state

Drug: elafibranor; Drug: CHRONO-INDOCID

Interventions

elafibranor DRUG

Elafibranor 120mg is a coated tablet for oral administration

Also known as: GFT505

DDI

CHRONO-INDOCID DRUG

CHRONO-INDOCID 75mg is a capsule for bis in die (bid) oral administration

Also known as: Indomethacin

DDI

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Only males are eligible
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to the conduct of any study related procedures;
• Healthy Caucasian male participant, aged between 18 and 50 years (inclusive);

You may not qualify if:

• Participants presenting with any of the following criteria will not be included in the trial:
• Any history or presence of significant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious disease or malignant tumor. Specific attention should be paid for history or presence of any hemorrhage/ulceration of the GI tract;
• 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 except that appendectomy and hernia repair will be allowed. Bariatric surgery will not be allowed;
• Major surgery within 28 days prior to screening or major surgery planned within 6 months following participation to the study;
• Frequent headaches (\>2 times /month) and / or migraine, recurrent nausea and / or vomiting;
• 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;
• General anesthetics within the 3 months prior to first administration;
• History or presence of any allergy or unusual reactions to drugs or anesthetics or known hypersensibility to the investigational products (elafibranor and/or CHRONO-INDOCID®) or their excipients;
• Any medication that may interfere with study medications absorption, distribution, metabolism or excretion or could lead to induction or inhibition of microsomial enzymes within 3 months prior to first administration;
• Any history or suspicion of consumption of any drug of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methamphetamines, methadone, methylenedioxymethamphetamine (MDMA), opiates, tricyclic antidepressant) or alcohol (alcohol consumption \> 40 grams/day), from Screening to end of the study;
• Positive for hepatitis B or hepatitis C, or positive results for HIV 1 or 2 tests;
• Participant unable to abstain from intensive muscular effort;
• Participant who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development;
• Participant who, considering the indemnities of the present study, would have received more than 4500 Euros for his participation in biomedical research within the 12 last months, including the indemnities for the present study;
• Participant who cannot be contacted in case of emergency;

Sponsors & Collaborators

• Genfit: lead

Study Sites (1)

Eurofins Optimed Clinical Pharmacology Unit

Gières, 38610, France

Location

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pascal Birman, MD

  Genfit

  STUDY DIRECTOR

Study Design

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

Model Details: Open-label, one sequence crossover, single-centre, single group assignment Phase 1 study in healthy male Caucasians volunteers, aged between 18-50 years old (inclusive)

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 14, 2019
• Study Start: September 23, 2019
• Primary Completion: March 15, 2020
• Study Completion: March 31, 2020
• Last Updated: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)