Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers
Phase 1
Terminated
- Conditions
- Viral Hepatitis BChronic Hepatitis BHepatitis B
- Interventions
- Registration Number
- NCT03032536
- Lead Sponsor
- Alios Biopharma Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 54
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment K AL-3778 Part 3: AL-3778 twice daily and tenofovir disoproxil fumarate 300 mg once daily both administered under fasted conditions for 14 days. AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages: * 600mg: 2 x 300-mg OR * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg Treatments A, B, C AL-3778 Part 1: Cross-Over * Treatment A: AL-3778 6 x 100-mg capsules (fasted) once. * Treatment B: AL-3778 2 x 300-mg tablets (fasted) once * Treatment C: AL-3778 2 x 300-mg tablets (high-fat meal) once. Treatments D, E, F AL-3778 Part 2 (optional): Cross-Over * Treatment D: AL-3778 2×300-mg tablets (fasted) once. * Treatment E: AL-3778 tablet Dose (fasted) once. Dose will match Treatment F dose and will be: * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg * Treatment F: AL-3778 tablet Dose (high-fat meal) once. Dose will match Treatment E dose and will be: * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg Treatment G AL-3778 Part 3: AL-3778 twice daily administered under fasted conditions for 14 days. Dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages: * 600mg: 2 x 300-mg OR * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg Treatment I AL-3778 Part 3: AL-3778 twice daily with entecavir 0.5 mg once daily both administered under fasted conditions for 14 days. AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages: * 600mg: 2 x 300-mg OR * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg Treatment H Entecavir Part 3: Entecavir 0.5 mg once daily administered under fasted conditions for 14 days Treatment I Entecavir Part 3: AL-3778 twice daily with entecavir 0.5 mg once daily both administered under fasted conditions for 14 days. AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages: * 600mg: 2 x 300-mg OR * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg Treatment J Tenofovir disoproxil fumarate Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days Treatment K Tenofovir disoproxil fumarate Part 3: AL-3778 twice daily and tenofovir disoproxil fumarate 300 mg once daily both administered under fasted conditions for 14 days. AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages: * 600mg: 2 x 300-mg OR * 1000mg: 2 x 500-mg OR * 800mg: 1 x 300-mg + 1 x 500-mg OR * 700mg: 1 x 200-mg + 1 x 500-mg
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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 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 Changes in Vital Signs during and after study drug administration Day 1 to Day 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
Trial Locations
- Locations (2)
Auckland Clinical Studies
🇳🇿Auckland, New Zealand
Christchurch Clinical Studies Trust
🇳🇿Christchurch, New Zealand