Drug Drug Interaction Study for EYP001 With Entecavir
Drug Drug Interaction Study for EYP001 With Entecavir
This is a Phase 1, single-center, open-label, three subsequent dosing periods study to
 evaluate the drug-drug-interaction (DDI), pharmaco-kinetics (PK) and pharmacodynamics (PD),
 safety, and tolerability of a single dose of EYP100a combined with ETV in healthy men and
 women dosed in the morning under fasted conditions.
This is a Phase 1, single-center, open-label, three consecutive dosing periods study to
 evaluate the drug-drug interaction, PK, safety, tolerability and PD of a single dose of
 EYP100a combined with ETV in healthy men and women. Sixteen (16) adult male and female
 healthy participants 18 to 60 years of age inclusive are planned to participate in the study.
 Women of childbearing potential will be eligible to participate if she is non pregnant or non
 lactating and willing to use adequate contraception.

 All participants in the study will be monitored for safety after administration of the last
 dose of investigational product and with a follow up visit. The DDI, PK, PD, safety and
 tolerability of EYP001a and ETV will be assessed based on plasma-concentration profiles of
 EYP001a and ETV, FXR related PD markers and the types and frequency of treatment-emergent
 adverse events (TEAEs) reported, concomitant medication usage, and changes from baseline in
 physical examination (PE), vital signs, electrocardiogram (ECG), and standard clinical
 laboratory tests.
Inclusion Criteria:

 -  Subject has provided written consent

 -  In the investigator's opinion, the subject is able to understand and comply with
 protocol requirements, instructions, and study restrictions and is likely to complete
 the study as planned

 -  Subject is in good health as deemed by the investigator, based on the findings
 following a medical evaluation, including medical history, physical examination,
 laboratory tests and single ECG

 -  Male or female, 18-60 years of age inclusive

 -  Body mass index 18.0-35.0 kg/m2, inclusive. The minimum weight is 50 kg, the maximum
 is 115 kg.

 -  A female subject is eligible to participate in this study if:

 1. 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

 2. She is of childbearing potential and is non pregnant or non lactating and willing
 to use adequate contraception from screening until 6 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. Periodic abstinence (e.g., calendar,
 ovulation, symptothermal, or postovulation methods) and withdrawal are not
 acceptable methods of contraception

 3. 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. Periodic abstinence (e.g., calendar, ovulation,
 symptothermal, or postovulation methods) and withdrawal are not acceptable
 methods of contraception.

 -  If male, subject is surgically sterile or practicing required forms of birth control
 until 6 months after the last dose of the study drug(s). Males must agree to refrain
 from sperm donation from check-in through 6 months after the last dose of the study
 drug(s)

 -  Subject does not use nicotine or nicotine-containing products during study
 participation.

 Exclusion Criteria:

 -  Subject is mentally or legally incapacitated, has significant emotional problems at
 the time of prestudy (screening) visit or expected during the conduct of the study or
 has a history of a clinically significant psychiatric disorder over the last 5 years.

 -  Subject has a history of any illness that, in the opinion of the investigator, would
 confound the objectives or results of the study or poses an additional risk to the
 subject by their participation in the study

 -  Subject has an estimated creatinine clearance of ≤ 80 mL/min based on the
 Cockcroft-Gault equation; subjects who have an actual or estimated creatinine
 clearance within 10% of 80 mL/min may be enrolled in the study at the discretion of
 the investigator.

 -  Pregnant or nursing (lactating) females, confirmed by a positive human chorionic
 gonadotropin laboratory test or females contemplating pregnancy. Men whose female
 partners are pregnant or contemplating pregnancy from the date of screening until 6
 months after their last dose of study drugs

 -  Clinically significant cardiovascular, respiratory, skeletal, renal, gastrointestinal,
 hematologic, hepatic, immunological, neurologic, endocrine, genitourinary
 abnormalities or disease or any other medical illness as determined by the
 investigator or Sponsor's Medical Monitor

 -  Subject has a history of malignancy except completely excised basal cell carcinoma or
 squamous cell carcinoma of the skin

 -  Subject lacks or has poor peripheral venous access

 -  Positive screening result for hepatitis B, hepatitis C and/or HIV serology

 -  Any condition that, in the opinion of the investigator, would compromise the study's
 objectives or the well-being of the subject or prevent the subject from meeting the
 study requirements

 -  Clinically significant abnormal ECG findings. Particularly, a history or family
 history of prolonged QT syndrome (eg, torsades de pointes) or sudden cardiac death.

 -  ECG with PR >220 ms, QRS >120 ms, QTcF >450 ms, as assessed by 12-lead ECG at the
 screening visit

 -  Subject has had major surgery, or clinically significant blood loss or elective blood
 donation of significant volume (ie, >500 mL) within 60 days of first dose of study
 drug; >1 unit of plasma within 7 days of first dose of study drug

 -  Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of
 the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes
 of rest). One repeat measurement after an additional 5 minutes of rest is permitted

 -  Evidence of active infection

 -  Unwilling to abstain from alcohol for at least 48 hours prior Day 1 through to the end
 of the study

 -  History of regular alcohol intake >7 units per week of alcohol for females and >14
 units per week for males (one unit is defined as 10 g alcohol) within 3 months of the
 screening visit

 -  The subject has a positive screening for drugs of abuse on Day -1 or Day 9 at check in
 prior to the start of the confinement periods.

 -  The use of concomitant medications, including prescription, over the counter
 medications, and herbal medications (such as St. John's Wort [Hypericum perforatum])
 (except for HRT patches, combined oral contraceptive pills and Progesterone IUD)
 within 30 days prior to the first dose of study medication is excluded, unless
 approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen/paracetamol
 (acetaminophen) is permitted

 -  Subject has received an investigational drug (including investigational vaccines) or
 used an invasive investigational medical device within 90 days before the planned
 study drug

 -  Subject has a history of significant* multiple and/or severe allergies

 -  Hypersensitivity to the active substances or to any of the excipients of EYP001a and
 or ETV

 -  Abnormal biochemistry or hematology laboratory results obtained at screening
 determined to be clinically significant by the Investigator. Screening ALT, AST, GGT,
 albumin, and total bilirubin must be within normal ranges. Creatine kinase >1.5 x ULN
 is exclusionary

 -  Unwillingness or inability to comply with the study protocol for any other reason.