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This is a single centre, open label, randomized, 3 treatment arms, with and without food dosing, Phase 1b pharmacology study to assess the safety, tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Farnesoid X Receptor (FXR) agonist/modulator EYP001a in healthy volunteers and Nonalcoholic Steatohepatitis (NASH) patients.
In total 16 participants (4 healthy volunteers and 12 NASH patients) will be enrolled and randomly assigned to one of the 3 treatment arms:
Subsequently, all the enrolled participants (both healthy volunteers and NASH patients) will be randomly assigned to one of the 2 parallel study Groups:
The maximum total engagement duration for eligible participants in this study is up to 76 days: 60 days screening, 1-day admission visit and 8 days dosing period (in-patient in clinical trial unit) and 7 days follow-up.
The participants who are eligible for enrolment will be admitted to the Clinical Trial Unit on Day 1. The participants will receive EYP001a at the study site by trained personnel per the schedule of dosing for the study from Day 2 to Day 9 in fed/fasted state depending upon the study group. Participants will be discharged on the morning (8:00 AM) of Day 10 after collection of last PK and PD blood samples. Participants will return to the Clinical Trial Unit on Day 16 for the follow-up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1: EYP001a Dose A | Experimental | Dose A once daily morning dose |
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| 2: EYP001a Dose B | Experimental | Dose B once daily morning dose |
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| 3: EYP001a Dose C | Experimental | Dose C twice daily - first dose morning dose and second dose 3 hours post first dose |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EYP001a | Drug | Oral tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of EYP001a | Day 2 through day 9 | |
| Time to reach maximum concentration (Tmax) after EYP001a administration | Day 2 through day 9 | |
| Area under the concentration-time curve (AUC) from time 0 to last measurable concentration (AUC0-10h and AUClast) of EYP001a | Day 2 through day 9 | |
| Area under the concentration-time curve (AUC) and Maximum plasma concentration (Cmax) ratios | Day 2 through day 9 | |
| Type and frequencies of Adverse events | Day 1 through day 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one) | pg/mL (picogram per milliliter). These will be measured in plasma samples using a validated method | Day 2 through day 9 |
| Bile acid precursor : Fibroblast growth factor 19 (FGF19) |
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Inclusion Criteria:
Have given voluntary written informed consent;
Male/female participants aged 18 years to 75 years with a Body Mass Index (BMI) ≥ 25 kg/m² and ≤ 45 kg/m² at screening.
A female participant is eligible to participate in this study if:
Have Alanine Aminotransferase (ALT) >1.5 upper limit of normal (ULN) during screening period.
Fibroscan® Vibration-Controlled Transient Elastography (VTCE) liver stiffness (liver stiffness measure (LSM) for >8.5 kPa) and steatosis (Controlled Attenuation Parameter (CAP) ≥250 decibels per meter (dB/m)).
Normal liver function at screening for alkaline phosphatase (ALP), Total Bilirubin (TBL), conjugated Bilirubin, platelets, International normalized ratio (INR).
Nota Bene: Criteria 4 and 5 do not apply to healthy volunteers.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ENYO Pharma clinical site | Randwick | New South Wales | Australia |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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mg/mL (milligram per milliliter). These will be measured in plasma samples using a validated method
| Day 2 through day 9 |
| Total Bile acids (secondary and primary) | These will be measured in plasma samples using a validated method | Day 1 through day 9 |