Healthy
Conditions
Brief summary
The farnesoid X receptor (FXR) regulates hepatitis B virus replication through the bile acids pathway. EYP001a is a selective, synthetic FXR agonist under development for the treatment of hepatitis B. This Phase 1 study is designed primarily to evaluate the single ascending dose (SAD) followed by a multiple ascending dose (MAD) safety, tolerability, and pharmacokinetics of EYP001a in healthy male subjects.
Detailed description
This is a two-part, randomized, double-blind, placebo-controlled study. Healthy male subjects will be randomly assigned to receive EYP001a or placebo. In the SAD part, up to 6 cohorts will receive EYP001a single doses of 30 mg, 60 mg, 120 mg, 250 mg, 500 mg, and 800 mg. In the MAD part, 4 cohorts will receive EYP001a doses of 60, 120, 250 and 500 mg, once daily for 14 days over 15-day period. Each cohort will include 6 active & 2 placebo subjects. Dose escalation will depend on evaluation of safety parameters. Participation will include up to 21-day screening period followed by dosing period (1 to 15 days). A follow-up evaluation will occur at 6 ± 2 days post final dose. Safety and tolerability will be assessed by monitoring adverse events, laboratory values, ECG parameters, and vital signs.
Interventions
DRUGEYP001a
10 mg and 100 mg capsules. Number of capsules to be ingested will depend on the dose cohort. Administered orally once daily. Single dose (SAD) or 14 days treatment (MAD).
DRUGPlacebo
Placebo capsules, identical in appearance to the EYP001a 10 mg and 100 mg capsules.
Sponsors
PRA Health Sciences
Enyo Pharma
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind study
Intervention model description
Planned single doses of 30 mg, 60 mg, 120 mg, 250 mg, 500 mg, and 800 mg, and planned multiple doses of 60 mg, 120 mg, 250 mg, and 500 mg, of EYP001a will be explored in this study. Subjects will be enrolled in dose escalation cohorts that will occur sequentially based upon review of safety and PK parameters.
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
\- Subjects must satisfy all of the following inclusion criteria during screening to be enrolled in the study: 1. Subject has given voluntary written informed consent before performance of any study related procedure 2. Subject must be 18 to 50 years of age, inclusive at screening 3. Subject must have clinical chemistries, hematology, and urinalysis tests within normal, allowable limits (if out of range must be considered clinically significant to be exclusionary) and performed within 21 days of receiving first dose of study drug 4. Subject must have a body mass index of between 18 and 30 kg/m2 at screening 5. Subject must have weight \> 60 kg at screening 6. Subject must have normal vital signs after 5 minutes resting in supine position at screening: * 95 mm Hg \< systolic blood pressure \< 140 mm Hg * 45 mm Hg \< diastolic blood pressure \< 90 mm Hg * 40 bpm \< pulse rate \< 90 bpm 7. Subject must have a normal 12-lead automatic ECG (incomplete right bundle branch block can be accepted): 120 ms \< PR \< 210 ms, QRS \< 120 ms, corrected QT interval (QTc) (Fridericia) ≤ 450 msec at screening. 8. Agree to abstain from all medication, including non-prescription and prescription medication (including vitamins and natural or herbal remedies, e.g. St. John's Wort) for 21 days before the first study day until discharge from the study (end of post study medical). 9. Subject agrees to use condom from dosing through 90 days after the dose of study drug. Female partners of male subjects enrolled into this study are also recommended to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device,diaphragm, condom, or abstinence).
Exclusion criteria
\- Subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of subjects reported with adverse events, serious adverse events | 7 days (SAD) or 21 days (MAD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of EYP001 | Days 1 & 2 (SAD and MAD). Days 14 & 15 (MAD) | ng/mL |
| Time to reach maximum concentration after drug administration (Tmax) of EYP001 | Days 1 & 2 (SAD and MAD). Days 14 & 15 (MAD) | hours |
| Area under the plasma concentration-time profile (AUCtau) of EYP001 | Days 1 & 2 (SAD and MAD). Days 14 & 15 (MAD) | ng.h/mL |
| C4 (7α-hydroxy-4-cholesten-3-one) | Days 1 & 2 (SAD). Days 1, 7 & 15 (MAD) | ng/mL |
| fibroblast growth factor 19 Fibroblast growth factor 19 (FGF19) | Days 1 & 2 (SAD). Days 1, 7 & 15 (MAD) | pg/mL |
Outcome results
None listed