Phase 1, Open-label, Partially Randomized, Parallel-group Study in Healthy Adult Subjects to Assess the Relative Bioavailability of Single-dose Simeprevir (SMV), Odalasvir (ODV), and AL-335 Administered as a Fixed-dose Combination (FDC) Compared With the Single Agents Administered Together, and to Assess the Effect of Multiple-dose Lansoprazole or Omeprazole on the Single-dose Pharmacokinetics of SMV, ODV, and AL-335 Administered as an FDC
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Part 2: Maximum Observed Plasma Concentration (Cmax) of SMV
Study Overview
Brief Summary
The purpose of this study is to assess the relative bioavailability of single-dose Simeprevir (SMV), Odalasvir (ODV), and AL-335 when administered as a fixed-dose combination (FDC) compared with the single agents when administered together, and to assess the effect of multiple-dose lansoprazole and omeprazole on the single-dose pharmacokinetics (PK) of SMV, ODV, and AL-335 when administered as an FDC.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Participant must have a body mass index (BMI: weight in kg divided by the square of height in meters) of 18.0 to 32.0 kilogram per meter (kg/m^2), extremes included, and a body weight not less than 50.0 kg
- •Participant must have a blood pressure (supine after at least 5 minutes rest) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted. Participants with a normal value at retest may be included
- •Participant must have a normal 12-lead Electrocardiogram [ECG] (based on the mean value of triplicate ECG parameters) consistent with normal cardiac conduction and function at screening, including:a) normal sinus rhythm (heart rate (HR) between 60 and 90 beats per minute [bpm], extremes included); b) QT interval corrected for heart rate according to Fridericia's formula (QTcF) less than or equal to <=450 milliseconds (ms) for male participants and <=470 ms for female participants; c) QRS interval <=110 ms; d) PR interval <=200 ms; e) Electrocardiogram (ECG) morphology consistent with healthy cardiac conduction and function. Any evidence of heart block is exclusionary. Any evidence of left or right bundle branch block is exclusionary
- •Female participant must have a negative highly sensitive urine or serum pregnancy test at Day -1
Exclusion Criteria
- •Participant with a past history of: a) Heart arrhythmias (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary; b) Risk factors associated with Torsade de Pointes such as hypokalemia; c) Family history of short/long QT syndrome; d) Sudden unexplained death (including sudden infant death syndrome) in a first degree relative (that is, sibling, offspring, or biological parent)
- •Participant has known allergies, hypersensitivity, or intolerance to odalasvir (ODV), AL-335, simeprevir (SMV), lansoprazole, or omeprazole, or their excipients
- •Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
- •Participant has a history of human immunodeficiency virus (HIV-1) or -2 infection positive, or tests positive for HIV-1 or -2 at screening
- •Participant has previously been dosed with SMV, ODV, or AL-335 in more than 3 single-dose studies or in a multiple dose study with SMV, ODV, or AL-335
Arms & Interventions
Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as a fixed-dose combination (FDC) tablet (G008 formulation) after a standardized breakfast on Day 1.
Intervention: Simeprevir 75 mg (Drug)
Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as a fixed-dose combination (FDC) tablet (G008 formulation) after a standardized breakfast on Day 1.
Intervention: Odalasvir 25 mg (Drug)
Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as a fixed-dose combination (FDC) tablet (G008 formulation) after a standardized breakfast on Day 1.
Intervention: AL-335 800 mg (Drug)
Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]
Participants will receive single oral dose of SMV 75 mg, ODV 12.5 mg, and AL-335 800 mg, given as an FDC tablet (G007 formulation) after a standardized breakfast on Day 1.
Intervention: Simeprevir 75 mg (Drug)
Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]
Participants will receive single oral dose of SMV 75 mg, ODV 12.5 mg, and AL-335 800 mg, given as an FDC tablet (G007 formulation) after a standardized breakfast on Day 1.
Intervention: Odalasvir 12.5 mg (Drug)
Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]
Participants will receive single oral dose of SMV 75 mg, ODV 12.5 mg, and AL-335 800 mg, given as an FDC tablet (G007 formulation) after a standardized breakfast on Day 1.
Intervention: AL-335 800 mg (Drug)
Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents after a standardized breakfast on Day 1.
Intervention: Simeprevir 75 mg (Drug)
Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents after a standardized breakfast on Day 1.
Intervention: Odalasvir 25 mg (Drug)
Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents after a standardized breakfast on Day 1.
Intervention: AL-335 800 mg (Drug)
Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]
Participants will receive 30 mg lansoprazole once daily in the morning under fasted conditions on Days 1 to 4, and together with a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast, which is served 2 hours after lansoprazole dosing, on Day 5.
Intervention: Simeprevir 75 mg (Drug)
Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]
Participants will receive 30 mg lansoprazole once daily in the morning under fasted conditions on Days 1 to 4, and together with a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast, which is served 2 hours after lansoprazole dosing, on Day 5.
Intervention: Odalasvir 25 mg (Drug)
Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]
Participants will receive 30 mg lansoprazole once daily in the morning under fasted conditions on Days 1 to 4, and together with a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast, which is served 2 hours after lansoprazole dosing, on Day 5.
Intervention: AL-335 800 mg (Drug)
Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]
Participants will receive 30 mg lansoprazole once daily in the morning under fasted conditions on Days 1 to 4, and together with a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast, which is served 2 hours after lansoprazole dosing, on Day 5.
Intervention: Lansoprazole 30 mg (Drug)
Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]
Participants will receive 20 mg omeprazole once daily in the morning immediately before a (non-standardized) breakfast on Days 1 to 4, and immediately before a standardized breakfast and within 1 hour before a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast on Day 5. Treatment E will only be started in case a drug-drug interaction (DDI) is observed for Treatment D.
Intervention: Simeprevir 75 mg (Drug)
Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]
Participants will receive 20 mg omeprazole once daily in the morning immediately before a (non-standardized) breakfast on Days 1 to 4, and immediately before a standardized breakfast and within 1 hour before a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast on Day 5. Treatment E will only be started in case a drug-drug interaction (DDI) is observed for Treatment D.
Intervention: Odalasvir 25 mg (Drug)
Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]
Participants will receive 20 mg omeprazole once daily in the morning immediately before a (non-standardized) breakfast on Days 1 to 4, and immediately before a standardized breakfast and within 1 hour before a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast on Day 5. Treatment E will only be started in case a drug-drug interaction (DDI) is observed for Treatment D.
Intervention: AL-335 800 mg (Drug)
Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]
Participants will receive 20 mg omeprazole once daily in the morning immediately before a (non-standardized) breakfast on Days 1 to 4, and immediately before a standardized breakfast and within 1 hour before a single oral dose of an FDC containing 75 mg SMV, 25 mg ODV, and 800 mg AL-335 (G008 formulation) after a standardized breakfast on Day 5. Treatment E will only be started in case a drug-drug interaction (DDI) is observed for Treatment D.
Intervention: Omeprazole 20 mg (Drug)
Part 2: Treatment Sequence A2-F
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as an FDC (Treatment A2 - G008 formulation) on Day 1 of Period 1, and then single oral dose of SMV 75 mg, ODV 25 mg, and AL-335 800 mg, given as an FDC (Treatment F - G012 formulation) on Day 1 of Period 2, under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence A2-F
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as an FDC (Treatment A2 - G008 formulation) on Day 1 of Period 1, and then single oral dose of SMV 75 mg, ODV 25 mg, and AL-335 800 mg, given as an FDC (Treatment F - G012 formulation) on Day 1 of Period 2, under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence A2-F
Participants will receive single oral dose of simeprevir (SMV) 75 milligram (mg), odalasvir (ODV) 25 mg, and AL-335 800 mg, given as an FDC (Treatment A2 - G008 formulation) on Day 1 of Period 1, and then single oral dose of SMV 75 mg, ODV 25 mg, and AL-335 800 mg, given as an FDC (Treatment F - G012 formulation) on Day 1 of Period 2, under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence F-A2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment A2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence F-A2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment A2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence F-A2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment A2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence C2-F
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents (Treatment C2) on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence C2-F
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents (Treatment C2) on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence C2-F
Participants will receive single oral dose of 75 mg SMV, 25 mg ODV, and 800 mg AL-335, given as 3 single agents (Treatment C2) on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence F-C2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence F-C2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence F-C2
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence C2-G
Participants will receive Treatment C2 on Day 1 of Period 1 and then 2 tablets of SMV 37.5 mg, ODV 37.5 mg, and AL-335 400 mg, given as FDC (Treatment G - G013 formulation) on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence C2-G
Participants will receive Treatment C2 on Day 1 of Period 1 and then 2 tablets of SMV 37.5 mg, ODV 37.5 mg, and AL-335 400 mg, given as FDC (Treatment G - G013 formulation) on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence C2-G
Participants will receive Treatment C2 on Day 1 of Period 1 and then 2 tablets of SMV 37.5 mg, ODV 37.5 mg, and AL-335 400 mg, given as FDC (Treatment G - G013 formulation) on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 75 mg (Drug)
Part 2: Treatment Sequence C2-G
Participants will receive Treatment C2 on Day 1 of Period 1 and then 2 tablets of SMV 37.5 mg, ODV 37.5 mg, and AL-335 400 mg, given as FDC (Treatment G - G013 formulation) on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence G-C2
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence G-C2
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence G-C2
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 75 mg (Drug)
Part 2: Treatment Sequence G-C2
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment C2 on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence F-G
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment G on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence F-G
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment G on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence F-G
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment G on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 75 mg (Drug)
Part 2: Treatment Sequence F-G
Participants will receive Treatment F on Day 1 of Period 1 and then Treatment G on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Part 2: Treatment Sequence G-F
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Simeprevir 75 mg (Drug)
Part 2: Treatment Sequence G-F
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 25 mg (Drug)
Part 2: Treatment Sequence G-F
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: Odalasvir 75 mg (Drug)
Part 2: Treatment Sequence G-F
Participants will receive Treatment G on Day 1 of Period 1 and then Treatment F on Day 1 of Period 2 under fed condition (after a standardized breakfast). A washout period of at least 2 weeks will be maintained between each treatment.
Intervention: AL-335 800 mg (Drug)
Outcomes
Primary Outcomes
Part 2: Maximum Observed Plasma Concentration (Cmax) of SMV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of SMV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of ODV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of SMV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV
Time Frame: Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 1: Analyte Concentration at 1 Hour Post Dosing (C1h) of Lansoprazole
Time Frame: Day 5 (1 hour post dose)
Analyte Concentration at 1 Hour Post Dosing (C1h) of Lansoprazole
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)
Time Frame: Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole
Time Frame: Day 5 (2 hour post dose)
Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole.
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of ODV
Time Frame: Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose
AUC (0-last) is the area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 1: Analyte Concentration at 1 Hour Post Dosing (C1h) of Omeprazole (if applicable)
Time Frame: Day 5 (1 hour post dose)
Analyte concentration will only be assessed if participants receive omeprazole (only in case a drug-drug interaction \[DDI\] is observed for participants who received lansoprazole).
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
Time Frame: Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-335
Time Frame: Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose
Cmax is defined as the maximum observed plasma concentration.
Part 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Omeprazole (if applicable)
Time Frame: Day 5 (2 hour post dose)
Analyte concentration will only be assessed if participants receive omeprazole (only in case an DDI is observed for participants who received lansoprazole).
Secondary Outcomes
- Part 2: Exposure as Measured by AUC From 2 Different Fixed Dose Combination Formulations containing odalasvir (ODV) (Treatment F Versus Treatment A2)(Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose)
- Part 1 and 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Screening (21 days prior to the first dose) to follow up Phase (30 to 35 days after last dose))