Drug-drug InteractionPhase 1NCT03985969
Study to Investigate the Potential Drug-Drug Interaction Between Elafibranor and Indomethacin
A Phase 1 study testing elafibranor and CHRONO-INDOCID in people with Drug-drug Interaction, run by Genfit at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug-drug Interaction
- What is being tested?
- elafibranor and CHRONO-INDOCID
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteFrance
- Study dates
- 23 Sep 2019to 31 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must meet all of the following inclusion criteria to be eligible for enrolment into the trial:
- Provide written informed consent prior to the conduct of any study related procedures;
- Healthy Caucasian male participant, aged between 18 and 50 years (inclusive);
- Non-smoker participant or smoker of not more than 5 cigarettes a day within one year prior to Inclusion visit;
- Body Mass Index (BMI) between 19 and 28 kg/m² and Body Weight (BW) not lower than 55 kg at both Screening visit and Inclusion visit;
- Considered as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination) at both Screening and Inclusion visits. This will include no variation of body weight of more than 5% between screening and inclusion visits;
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- Normal blood pressure (BP) and heart rate (HR) at both Screening and Inclusion visits after 5 minutes in supine position:
- 90 mmHg ≤ systolic blood pressure (SBP) ≤ 145 mmHg, 50 mmHg ≤ diastolic blood pressure (DBP) ≤ 90 mmHg, 45 bpm ≤ HR ≤ 90 bpm. Out-of-range values that are not clinically significant, as determined by the Investigator, may be repeated twice and the participant may be enrolled if at least 1 repeated value is within the specified ranges; 7. Normal electrocardiogram (ECG) recording on a 12-lead ECG at both Screening and Inclusion visits: 120 ≤ PR < 220 ms, QRS < 110 ms, QTcf ≤ 430 ms. No sign of any trouble of sinusal automatism, or considered as non clinically significant by the Investigator.
- Out-of-range values that are not clinically significant (as determined by the Investigator) may be repeated twice during Screening and Inclusion visits, and the participant may be enrolled if at least 1 repeated value is within the specified normal ranges; 8. Laboratory parameters within the normal range of the laboratory (haematological, blood chemistry tests, urinalysis) at Screening and Inclusion visits. Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator; 9. Participant with normal dietary habits; 10. Covered by Health Insurance System and in compliance with the recommendations of National Law in force relating to biomedical research.
Who cannot join
- 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;
- Symptomatic hypotension at both Screening and Inclusion visits, whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP (≥20mmHg) or DBP (≥10mmHg) within three minutes when changing from the supine to the standing position;
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- 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;
- Receipt of blood products within 2 months prior to Inclusion visit;
- 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 drug intake (except paracetamol 3g/d) during the last month prior to inclusion;
- A positive alcohol test result or urine screen for drugs of abuse result at Screening or Inclusion visits;
- 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;
- 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 within 48 hours before Inclusion visit and until end of study visit;
- 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 in the exclusion period of a previous study;
- 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;
- Participant with no legal capacity or limited legal capacity or unable to give an informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Open-label Study, in Healthy Male Volunteers to Evaluate the Potential Effect of Indomethacin on the Pharmacokinetics Parameters of Elafibranor
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
- Being tested
- elafibranor, CHRONO-INDOCID
- Keywords
- Healthy volunteers, Elafibranor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
elafibranorDrug
Also called GFT505
Elafibranor 120mg is a coated tablet for oral administration
CHRONO-INDOCIDDrug
Also called Indomethacin
CHRONO-INDOCID 75mg is a capsule for bis in die (bid) oral administration
| Study group | Role | What they receive |
|---|---|---|
| DDI | Experimental | Period 1: study of elafibranor's pharmacokinetics Period 2: study of elafibranor's pharmacokinetics under CHRONO-INDOCID® (indomethacin) at steady state Receives: Drug: elafibranor; Drug: CHRONO-INDOCID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞))
of elafibranor
Measured: 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
Measured: 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-∞))
of GFT1007
Measured: 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 GFT1007
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start23 Sep 2019
- Primary completion15 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug-drug InteractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Intervention model
- Sequential
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genfit
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pascal Birman, MD, Study director, Genfit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03985969
- Sponsor's protocol ID
- GFT505-119-15
- Other IDs
- 2019-001451-38, 2019
- Status last verified
- Aug 2020
- First submitted
- 11 Jun 2019
- Last updated
- 13 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open-label Study, in Healthy Male Volunteers to Evaluate the Potential Effect of Indomethacin on the Pharmacokinetics Parameters of Elafibranor
- ClinicalTrials.gov ID
- NCT03985969
- Acronym / sponsor ID
- GFT505-119-15
- Conditions
- Drug-drug Interaction
- Keywords
- Healthy volunteers, Elafibranor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- GenfitIndustry (pharma, biotech, devices)
- Study start
- 23 Sep 2019 (actual)
- Primary completion
- 15 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 14 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| DDI | Experimental | Drug: elafibranor, Drug: CHRONO-INDOCIDPeriod 1: study of elafibranor's pharmacokinetics Period 2: study of elafibranor's pharmacokinetics under CHRONO-INDOCID® (indomethacin) at steady state |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Participants must meet all of the following inclusion criteria to be eligible for enrolment into the trial:
- Provide written informed consent prior to the conduct of any study related procedures;
- Healthy Caucasian male participant, aged between 18 and 50 years (inclusive);
- Non-smoker participant or smoker of not more than 5 cigarettes a day within one year prior to Inclusion visit;
- Body Mass Index (BMI) between 19 and 28 kg/m² and Body Weight (BW) not lower than 55 kg at both Screening visit and Inclusion visit;
Key exclusion criteria (22 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| elafibranorAlso: GFT505Elafibranor 120mg is a coated tablet for oral administration | Drug | DDI |
| CHRONO-INDOCIDAlso: IndomethacinCHRONO-INDOCID 75mg is a capsule for bis in die (bid) oral administration | Drug | DDI |
Primary outcome
Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞))
Time frame: 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)
of elafibranor
Plasma pharmacokinetics: Maximum plasma drug concentration (Cmax)
Time frame: 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)
of elafibranor
2 secondary outcomes
Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞))
Time frame: 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)
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascal Birman, MD study director
Genfit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing elafibranor and CHRONO-INDOCID in people with Drug-drug Interaction, run by Genfit at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞)) (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2020.