Hepatitis B, ChronicPhase 1NCT03469583
Drug Drug Interaction Study for EYP001 With Entecavir
A Phase 1 study testing EYP001 and Entecavir 1 MG in people with Hepatitis B, Chronic, run by Enyo Pharma at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- EYP001 and Entecavir 1 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustralia
- Study dates
- 12 Feb 2018to 20 Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- 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 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
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Australia1 site
Cmax Clinical Research Pty Ltd
Adelaide, South Australia, 5000
About this study
Official title: Study of the Drug Interaction of EYP001a With Entecavir in Healthy Subjects
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.
Read the detailed description
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.
- Conditions
- Hepatitis B, Chronic
- Being tested
- EYP001, Entecavir 1 MG
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EYP001Drug
Also called EYP001a
EYP001 self administered capsules, morning, with non carbonated water
Entecavir 1 MGDrug
Also called ETV
Entecavir self administered tablets, morning, with non carbonated water
| Study group | Role | What they receive |
|---|---|---|
| EYP001 dose1 | Experimental | EYP001 capsules by mouth Receives: Drug: EYP001 |
| Entecavir 1mg | Active comparator | 2 tablets of 0.5mg, by mouth Receives: Drug: Entecavir 1 MG |
| EYP001 dose 1 + Entecavir 1mg | Experimental | EYP001 capsules and 2 tablets of Entecavir 0.5mg by mouth Receives: Drug: EYP001; Drug: Entecavir 1 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve
Area under the concentration-time curve from time 0 to 24 hours
Measured: 24 hrs
Secondary outcomes (8)
Adverse events
Treatment emergent adverse events
Measured: Day 1 to Day 12
Concentration maximum (peak)
highest concentration of EYP001 and ETV after dosing
Measured: Day 1, Day 3 and Day 10
Volume of distribution (Vz/F)
Pharmacokinetic endpoints
Measured: 8 days
Time to maximum concentration (Tmax)
Pharmacokinetic endpoints
Measured: 8 days
Terminal Elimination Rate Constant (kel)
Pharmacokinetic endpoints
Measured: 8 days
Terminal half-life (t1/2)
Pharmacokinetic endpoints
Measured: 8 days
Terminal clearance (CL/F)
Pharmacokinetic endpoints
Measured: 8 days
C4 and FGF19
C4 (7αhydroxy-4-cholesten-3- one) and fibroblast growth factor 19 (FGF19) are PD Marker of FXR engagement
Measured: Day 1, Day 3 and Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2018
- Study start12 Feb 2018
- Primary completion20 Jun 2018
- Study completion20 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Enyo Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Responsible party
- Sponsor
- Investigators
- Angela Molga, M.D. FRACP, Principal investigator, CMAX - Clinical Research Pty Ltd, Level 5, 18a North Terrace, Adelaide, South Australia, 5000, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03469583
- Sponsor's protocol ID
- EYP001-104
- Status last verified
- Jul 2018
- First submitted
- 29 Jan 2018
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Drug Interaction of EYP001a With Entecavir in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03469583
- Acronym / sponsor ID
- EYP001-104
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Enyo PharmaIndustry (pharma, biotech, devices)
- Collaborators
- CPR Pharma Services Pty Ltd, Australia
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 20 Jun 2018 (actual)
- Study completion
- 20 Jul 2018 (actual)
- First posted
- 19 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EYP001 dose1 | Experimental | Drug: EYP001EYP001 capsules by mouth |
| Entecavir 1mg | Active comparator | Drug: Entecavir 1 MG2 tablets of 0.5mg, by mouth |
| EYP001 dose 1 + Entecavir 1mg | Experimental | Drug: EYP001, Drug: Entecavir 1 MGEYP001 capsules and 2 tablets of Entecavir 0.5mg by mouth |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EYP001Also: EYP001aEYP001 self administered capsules, morning, with non carbonated water | Drug | EYP001 dose 1 + Entecavir 1mg, EYP001 dose1 |
| Entecavir 1 MGAlso: ETVEntecavir self administered tablets, morning, with non carbonated water | Drug | EYP001 dose 1 + Entecavir 1mg, Entecavir 1mg |
Primary outcome
Area Under the Curve
Time frame: 24 hrs
Area under the concentration-time curve from time 0 to 24 hours
8 secondary outcomes
Adverse events
Time frame: Day 1 to Day 12
Concentration maximum (peak)
Time frame: Day 1, Day 3 and Day 10
Volume of distribution (Vz/F)
Time frame: 8 days
Time to maximum concentration (Tmax)
Time frame: 8 days
Terminal Elimination Rate Constant (kel)
Time frame: 8 days
Terminal half-life (t1/2)
Time frame: 8 days
Terminal clearance (CL/F)
Time frame: 8 days
C4 and FGF19
Time frame: Day 1, Day 3 and Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Molga, M.D. FRACP principal investigator
CMAX - Clinical Research Pty Ltd, Level 5, 18a North Terrace, Adelaide, South Australia, 5000, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EYP001 and Entecavir 1 MG in people with Hepatitis B, Chronic, run by Enyo Pharma at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve (time frame: 24 hrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.