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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Auckland Clinical Studies
Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax)
Time frame: 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)
Time frame: 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∞)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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: Predose plasma concentrations (C_0-h)
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Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Screening to Day 22
Changes in Vital Signs during and after study drug administration
Time frame: Day 1 to Day 22
changes in physical examinations during and after study drug administration
Time frame: Day 1 to Day 22
changes in clinical laboratory results during and after study drug administration
Time frame: Day 1 to Day 22
changes in electrocardiogram results during and after study drug administration
Time frame: Day 1 to Day 22