EYP001a Food Effect Study in Subjects With Chronic Hepatitis B Virus (HBV) Infection

NCT03320616 | Completed Phase 1

• 2 other identifiers: EYP001-1022016-004713-27
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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 assess Pharmacokinetics (PK) under fed and fasted conditions, and to assess the safety, tolerability and Pharmacodynamics (PD) of single oral doses of EYP001a in subjects with chronic HBV infection.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Type and frequencies of adverse events

  Day 1 of Period 1 through Day 7 to Day 9 of Period 2

Secondary Outcomes (5)

• Maximum observed plasma concentration (Cmax) of EYP001a

  Predose to 48 hours after dosing

• Time to attain maximum observed plasma concentration (Tmax) after EYP001a administration

  Predose to 48 hours after dosing

• Area under the plasma concentration-time curve (AUC)

  Predose to 48 hours after dosing

• Bile acid precursor C4 (7α hydroxy-4-cholesten-3-one)

  Predose to 48 hours after dosing

• Bile-regulating fibroblast growth factor 19 (FGF-19)

  Predose to 48 hours after dosing

Study Arms (4)

Sequence 1

EXPERIMENTAL

4 single doses of EYP001a: Period 1 first dose morning fasted, second dose morning fed; Period 2 first dose evening fasted, second dose evening fed

Drug: EYP001a

Sequence 2

EXPERIMENTAL

4 single doses of EYP001a: Period 1 first dose evening fasted, second dose evening fed; Period 2 first dose morning fasted, second dose morning fed

Drug: EYP001a

Sequence 3

EXPERIMENTAL

4 single doses of EYP001a: Period 1 first dose morning fed, second dose morning fasted; Period 2 first dose evening fed, second dose evening fasted

Drug: EYP001a

Sequence 4

EXPERIMENTAL

4 single doses of EYP001a: Period 1 first dose evening fed, second dose evening fasted; Period 2 first dose morning fed, second dose morning fasted

Drug: EYP001a

Interventions

EYP001a DRUG

Oral EYP001a capsules - 100 mg strength

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has given voluntary written informed consent before performance of any study related procedure
• Has documented chronic HBV infection (documented within 12 months of screening visit), with criteria at screening: hepatitis B surface antigen (HBsAg) ≥ 50 IU/mL; HBV DNA \> 100 IU/mL; hepatitis Be antigen (HBeAg) negative or positive
• Gender: male or female
• Age: 18-65 years, inclusive, at screening
• Body mass index (BMI): 17.0-35.0 kg/m2 inclusive, at screening
• Weight: \>60 kg for males and \>45 kg for females
• Has normal vital signs after at least 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 \< heart rate \< 90 bpm
• Has no clinically significant abnormal 12-lead automatic electrocardiogram (ECG) (incomplete right bundle branch block can be accepted) at screening: 120 ms \< PR-interval \< 210 ms, QRS-duration \< 120 ms, corrected QT interval (QTc) (Fridericia's) ≤ 450 msec for males and females
• Has ALAT ≤ 3 x upper limit of normal (ULN) at screening
• Has documented liver histology with Metavir score (F0, F1, F2 or F3) or liver fibrosis documented with non-invasive alternatives to liver biopsy (Fibroscan) or shear wave elastography (Aixplorer) value \< 14.6 kPa
• Agrees 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 28 days prior to (each) admission to the clinical research center until discharge, except for authorized medications such as hormonal contraceptives for females (registered in The Netherlands) and paracetamol. On a case-by-case basis, regular co-medication either as defined on the separate medication exception list or as documented by written approval from the Sponsor and the PI as acceptable prior to randomization, will not be considered as a deviation from this criterion. All other situations related to co-medications are considered as deviations
• At screening, females must be non-pregnant and non-lactating, or of non-childbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year postmenopausal \[amenorrhoea duration of 12 consecutive months); non-pregnancy will be confirmed for all females by a serum pregnancy test conducted at screening and at (each) admission to the clinical research center
• Female subjects of child-bearing potential, with a fertile male sexual partner, should be willing to use adequate contraception from screening until 90 days after the followup visit. Adequate contraception is defined as using hormonal contraceptives or an intrauterine 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 subject, is acceptable
• Male subjects, if not surgically sterilized, should be willing to use adequate contraception and not donate sperm from (first) admission to the clinical research center until 90 days after the follow-up visit. Adequate contraception for the male subject (and his female partner) is defined as using hormonal contraceptives or an intrauterine 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 subject is acceptable
• At screening, has no recent (\<3 months) history of any clinically significant conditions, which, in the opinion of the PI, would jeopardize the safety of the subject or impact the validity of the study results

You may not qualify if:

• Previous participation in the current study
• Employee of PRA or the Sponsor
• Currently receives or has received during the 60 days (or 5 half-lives of the specific drug, whichever is longer) before (first) admission to the clinical research center until (the last) discharge a nucleos(t)ide-analogue therapy or other anti HBV treatment (interferons, experimental anti HBV drugs or vaccines)
• Coinfection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
• Receives or plans to receive systemic immunosuppressive medications during the study or ≤2 months prior to the first study drug administration
• Receiving or planning to receive interferon (IFN) during the study or ≤12 months prior to the first study drug administration
• Has significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia
• Clinical diagnosis of substance abuse with alcohol (regular alcohol consumption \>21 units \[men\] and \>14 units \[women\] per week \[1 unit = ½ pint of beer, 25 mL shot of 40% spirit or a 125 mL glass of wine\]), narcotics, or cocaine ≤12 months prior to screening
• Has any known pre-existing medical or psychiatric condition that could interfere with the subject's ability to provide informed consent or participate in study conduct, or that may confound study findings.
• Has a history of clinically significant gastrointestinal disease, especially peptic ulcerations, gastrointestinal bleeding, ulcerative colitis, cholecystectomy, Crohn's disease or Irritable Bowel Syndrome, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, or cardiovascular disease or any other condition which, in the opinion of the PI, would jeopardize the safety of the subject or impact the validity of the study results
• Has had acute diarrhea or constipation in the 7 days before (first) admission to the clinical research center. Diarrhea will be defined as the passage of liquid feces and/or a stool frequency of \> 3 times per day. Constipation will be defined as a failure to open the bowels more frequently than every other day.
• Has a history of long QT syndrome
• Has participated in a drug study within 30 days prior to the first drug administration in the current study
• Has a positive drug and alcohol screen (opiates, methadone, cocaine, methamphetamines, amphetamines, ecstasy, barbiturates, benzodiazepines, tricyclic antidepressants, phencyclidine and alcohol)
• Any current or previous (ie, ≤12 months prior to screening) abuse of drugs such as opiates, cocaine, ecstasy, or intravenous amphetamines. Subjects who admit to occasional use of cannabis will not be excluded as long as they are able to abstain from cannabis when they are in the clinical research center.

Sponsors & Collaborators

• Enyo Pharma: lead
• PRA Health Sciences: collaborator

Study Sites (1)

PRA-EDS

Groningen, Netherlands

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeroen van de Wetering, MD

  PRA-EDS

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The subjects will be randomized to 1 of 4 treatment sequences.

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: October 25, 2017
• Study Start: February 10, 2017
• Primary Completion: October 12, 2017
• Study Completion: October 12, 2017
• Last Updated: March 5, 2018

Record last verified: 2018-03

Locations

NL (1)