Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EYP001a in Healthy Volunteers and Nonalcoholic Steatohepatitis Patients

NCT03976687 | Completed Phase 1 FDA Drug

• 1 other identifier: EYP001-107
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

NASH - Nonalcoholic Steatohepatitis; Healthy

Outcome Measures

Primary Outcomes (5)

• 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

Secondary Outcomes (3)

• Bile acid precursor : C4 (7αhydroxy-4-cholesten-3-one)

  Day 2 through day 9

• Bile acid precursor : Fibroblast growth factor 19 (FGF19)

  Day 2 through day 9

• Total Bile acids (secondary and primary)

  Day 1 through day 9

Study Arms (3)

1: EYP001a Dose A

EXPERIMENTAL

Dose A once daily morning dose

Drug: EYP001a

2: EYP001a Dose B

EXPERIMENTAL

Dose B once daily morning dose

Drug: EYP001a

3: EYP001a Dose C

EXPERIMENTAL

Dose C twice daily - first dose morning dose and second dose 3 hours post first dose

Drug: EYP001a

Interventions

EYP001a DRUG

Oral tablets

1: EYP001a Dose A; 2: EYP001a Dose B; 3: EYP001a Dose C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• She is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's reference range for postmenopausal females). A post-menopausal female receiving hormone replacement therapy (HRT) other than hormone replacement patches who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation. A post-menopausal female using Hormone Replacement patches who is willing to discontinue the patch 48 hours before Check in on Day -1 and until the completion of her End of Study visit is eligible for study participation.
• She is of childbearing potential and is non-pregnant or non-lactating and willing to use adequate contraception from screening until 3 months after the End of Study visit. Adequate contraception is defined as a progesterone only intra uterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Also, total abstinence in accordance with the lifestyle of the participant is acceptable.
• She is of childbearing potential and is non-pregnant or non-lactating and taking the combined oral contraceptive pill and willing to discontinue the combined oral contraceptive pill 7 days prior to check in on Day -1 and until the completion of her End of Study visit and use adequate contraception from the day of cessation. Adequate contraception is defined as a diaphragm or cervical cap together with a condom. Also, total abstinence in accordance with the lifestyle of the participant is acceptable.
• 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.

You may not qualify if:

• Employee of a contract research organization (CRO) participating in this study or the Sponsor.
• Patients with known non-NASH chronic liver disease (alcohol, autoimmune, Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), active hepatitis C virus (HCV)).
• Female with childbearing potential if no dual safe anti-contraception method can be provided.
• Renal impairment (participants with an estimated glomerular filtration rate (eGFR) computed from the Modification of Diet in Renal Disease (MDRD) formula of \< 60ml/min/1.73m² are excluded). Note: participants with mild renal impairment (eGFR \>60 ml/min and ≤90 ml/min) are eligible.
• Has clinically relevant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Has any known pre-existing medical or psychiatric condition that could interfere with the participant's ability to provide informed consent or participate in study conduct, or that may confound study findings.
• Has a history of clinically significant gastrointestinal (GI) disease, especially peptic ulcerations, GI bleeding, ulcerative colitis, Crohn's disease or Inflammatory Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results.
• Has participated in any drug study within 60 days prior to the first drug administration in the current study.
• Has had major surgery within 30 days prior to the first drug administration.
• Concomitant use of not listed drugs after discussion with Sponsor not admitted.
• Has a history of relevant drug and/or food allergies

Sponsors & Collaborators

• Enyo Pharma: lead

Study Sites (1)

ENYO Pharma clinical site

Randwick, New South Wales, Australia

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 6, 2019
• Study Start: June 11, 2019
• Primary Completion: May 25, 2020
• Study Completion: May 25, 2020
• Last Updated: September 25, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)