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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001451-38 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DDI | Experimental | Period 1: study of elafibranor's pharmacokinetics Period 2: study of elafibranor's pharmacokinetics under CHRONO-INDOCID® (indomethacin) at steady state |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| elafibranor | Drug | Elafibranor 120mg is a coated tablet for oral administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma pharmacokinetics: Area under curve from dosing time to infinity (AUC(0-∞)) | of GFT1007 | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma pharmacokinetics: Area under curve from dosing time to last measurement (AUC(0-t)) | of elafibranor and GFT1007 | 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) |
Inclusion Criteria:
Participants must meet all of the following inclusion criteria to be eligible for enrolment into the trial:
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.
Exclusion Criteria:
Participants presenting with any of the following criteria will not be included in the trial:
Only males are eligible
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| Name | Affiliation | Role |
|---|---|---|
| Pascal Birman, MD | Genfit | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eurofins Optimed Clinical Pharmacology Unit | Gières | 38610 | France |
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| ID | Term |
|---|---|
| C585906 | 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid |
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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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)
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| CHRONO-INDOCID | Drug | CHRONO-INDOCID 75mg is a capsule for bis in die (bid) oral administration |
|
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of GFT1007 |
| 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 and GFT1007 |
| 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) | of elafibranor and GFT1007 | 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: Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total area under the plasma concentration-time curve (%AUCextra) | of elafibranor and GFT1007 | 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: Apparent total clearance (CL/F) | 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: Apparent volume of distribution (Vd/F) | 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) |