Drug Drug Interaction Study for EYP001 With Entecavir

NCT03469583 | Completed Phase 1

• 1 other identifier: EYP001-104
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve

  Area under the concentration-time curve from time 0 to 24 hours

  24 hrs

Secondary Outcomes (8)

• Adverse events

  Day 1 to Day 12

• Concentration maximum (peak)

  Day 1, Day 3 and Day 10

• Volume of distribution (Vz/F)

  8 days

• Time to maximum concentration (Tmax)

  8 days

• Terminal Elimination Rate Constant (kel)

  8 days

Study Arms (3)

EYP001 dose1

EXPERIMENTAL

EYP001 capsules by mouth

Drug: EYP001

Entecavir 1mg

ACTIVE COMPARATOR

2 tablets of 0.5mg, by mouth

Drug: Entecavir 1 MG

EYP001 dose 1 + Entecavir 1mg

EXPERIMENTAL

EYP001 capsules and 2 tablets of Entecavir 0.5mg by mouth

Drug: EYP001; Drug: Entecavir 1 MG

Interventions

EYP001 DRUG

EYP001 self administered capsules, morning, with non carbonated water

Also known as: EYP001a

EYP001 dose 1 + Entecavir 1mg; EYP001 dose1

Entecavir 1 MG DRUG

Entecavir self administered tablets, morning, with non carbonated water

Also known as: ETV

EYP001 dose 1 + Entecavir 1mg; Entecavir 1mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Gender Eligibility Details: 8 males and 8 females.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Enyo Pharma: lead
• CPR Pharma Services Pty Ltd, Australia: collaborator

Study Sites (1)

Cmax Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

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

• Angela Molga, M.D. FRACP

  CMAX - Clinical Research Pty Ltd, Level 5, 18a North Terrace, Adelaide, South Australia, 5000, Australia

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 19, 2018
• Study Start: February 12, 2018
• Primary Completion: June 20, 2018
• Study Completion: July 20, 2018
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

AU (1)