The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03469583




Registration number
NCT03469583
Ethics application status
Date submitted
29/01/2018
Date registered
12/03/2018
Date last updated
24/07/2018

Titles & IDs
Public title
Drug Drug Interaction Study for EYP001 With Entecavir
Scientific title
Study of the Drug Interaction of EYP001a With Entecavir in Healthy Subjects
Secondary ID [1] 0 0
EYP001-104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EYP001
Treatment: Drugs - Entecavir 1 MG

Experimental: EYP001 dose1 - EYP001 capsules by mouth

Active Comparator: Entecavir 1mg - 2 tablets of 0.5mg, by mouth

Experimental: EYP001 dose 1 + Entecavir 1mg - EYP001 capsules and 2 tablets of Entecavir 0.5mg by mouth


Treatment: Drugs: EYP001
EYP001 self administered capsules, morning, with non carbonated water

Treatment: Drugs: Entecavir 1 MG
Entecavir self administered tablets, morning, with non carbonated water

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Curve - Area under the concentration-time curve from time 0 to 24 hours
Timepoint [1] 0 0
24 hrs
Secondary outcome [1] 0 0
Adverse events - Treatment emergent adverse events
Timepoint [1] 0 0
Day 1 to Day 12
Secondary outcome [2] 0 0
Concentration maximum (peak) - highest concentration of EYP001 and ETV after dosing
Timepoint [2] 0 0
Day 1, Day 3 and Day 10
Secondary outcome [3] 0 0
Volume of distribution (Vz/F) - Pharmacokinetic endpoints
Timepoint [3] 0 0
8 days
Secondary outcome [4] 0 0
Time to maximum concentration (Tmax) - Pharmacokinetic endpoints
Timepoint [4] 0 0
8 days
Secondary outcome [5] 0 0
Terminal Elimination Rate Constant (kel) - Pharmacokinetic endpoints
Timepoint [5] 0 0
8 days
Secondary outcome [6] 0 0
Terminal half-life (t1/2) - Pharmacokinetic endpoints
Timepoint [6] 0 0
8 days
Secondary outcome [7] 0 0
Terminal clearance (CL/F) - Pharmacokinetic endpoints
Timepoint [7] 0 0
8 days
Secondary outcome [8] 0 0
C4 and FGF19 - C4 (7ahydroxy-4-cholesten-3- one) and fibroblast growth factor 19 (FGF19) are PD Marker of FXR engagement
Timepoint [8] 0 0
Day 1, Day 3 and Day 10

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Cmax Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Enyo Pharma
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
CPR Pharma Services Pty Ltd, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03469583
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Angela Molga, M.D. FRACP
Address 0 0
CMAX - Clinical Research Pty Ltd, Level 5, 18a North Terrace, Adelaide, South Australia, 5000, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications