Chronic Hepatitis B, Hepatitis B, Viral Hepatitis B
Conditions
Brief summary
This is an open-label, randomized, multi-part study to evaluate the relative oral bioavailability of a tablet formulation of AL-3778 (formerly NVR 3-778) administered under fasted and fed conditions (Parts 1 and 2) and the drug-drug interaction between AL-3778 and entecavir or tenofovir disoproxil fumarate (Part 3).
Interventions
DRUGAL-3778
AL-3778 tablets or capsules
DRUGEntecavir
Entecavir once daily for 14 days
DRUGTenofovir disoproxil fumarate
Tenofovir disoproxil fumarate once daily for 14 days
Sponsors
Alios Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria for All Subjects: 1. Subject has provided written consent. 2. 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. 3. Subject is in good health as deemed by the investigator, based on the totality of findings following a medical evaluation, including medical history, physical examination, laboratory tests and ECG. 4. Male or female, 18-60 years of age. 5. Body mass index 18-30 kg/m2, inclusive. The minimum weight is 50 kg. 6. 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 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. 7. 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). 8. Subject has been a nonsmoker and has not used nicotine or nicotine-containing products for at least 6 months. 9. Subjects who participated in Part 1 and/or Part 2 may participate in subsequent Part(s) upon satisfactory completion of a posttreatment visit, 7 days (+2 days) following the subject's last dose, and provided they continue to meet all of the inclusion criteria and none of the
Exclusion criteria
. Main
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC∞) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 |
| AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 |
| AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-Τ, Day 1) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 |
| AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (C_min) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
Secondary
| Measure | Time frame |
|---|---|
| AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14 |
| AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14 |
| AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-Τ, Day 14) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 |
| Incidence, nature, and severity of adverse events | Screening to Day 22 |
| AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| changes in physical examinations during and after study drug administration | Day 1 to Day 22 |
| changes in clinical laboratory results during and after study drug administration | Day 1 to Day 22 |
| changes in electrocardiogram results during and after study drug administration | Day 1 to Day 22 |
| Changes in Vital Signs during and after study drug administration | Day 1 to Day 22 |
| AL-3778, entecavir, tenofovir: Predose plasma concentrations (C_0-h) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Last observed plasma concentration (C_last) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (T_max) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (T_last) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
| AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½) | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22 |
Countries
New Zealand
Outcome results
None listed