Study to Assess the Relative Bioavailability of Fixed-Dose Combination (FDC) Tablet (Simeprevir, Odalasvir and AL-335) Compared With Single Agents Administered Together, and to Assess the Effect of Multiple-Dose Lansoprazole or Omeprazole on Single-Dose Pharmacokinetics of SMV, ODV, and AL-335 (FDC)

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Terminated

CT.gov ID

NCT03059303

Collaborator

(none)

Enrollment

Location

Arms

2.1

Actual Duration (Months)

34.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Simeprevir 75 mg Drug: Odalasvir 25 mg Drug: Odalasvir 12.5 mg Drug: Odalasvir 75 mg Drug: AL-335 800 mg Drug: Lansoprazole 30 mg Drug: Omeprazole 20 mg	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 20, 2017

Actual Primary Completion Date :

Apr 24, 2017

Actual Study Completion Date :

Apr 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 12.5 mg Part 1: ODV 12.5 mg taken orally as a component of FDC tablet in Treatment B. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2. Drug: Lansoprazole 30 mg 30 mg lansoprazole once daily from Day 1 to Day 5. Other Names: Prevacid
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2. Drug: Omeprazole 20 mg 20 mg omeprazole once daily from Day 1 to Day 5.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: Odalasvir 75 mg Part 2: ODV 75 mg taken orally as a component of FDC tablet (2 tablets of 37.5 mg each) in Treatment G. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: Odalasvir 75 mg Part 2: ODV 75 mg taken orally as a component of FDC tablet (2 tablets of 37.5 mg each) in Treatment G. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: Odalasvir 75 mg Part 2: ODV 75 mg taken orally as a component of FDC tablet (2 tablets of 37.5 mg each) in Treatment G. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.
Experimental: 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.	Drug: Simeprevir 75 mg Part 1: Simeprevir (SMV) 75 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent capsule in Treatment C. Part 2: SMV 75 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 37.5 mg each), and G (2 tablets of 37.5 mg each), and as a single agent capsule in Treatment C2. Drug: Odalasvir 25 mg Part 1: Odalasvir (ODV) 25 mg taken orally as a component of FDC tablet in Treatment A, D and E and as a single agent tablet in Treatment C. Part 2: ODV 25 mg taken orally as a component of FDC tablet in Treatment A2 and F (2-tablets of 12.5 mg each), and as a single agent tablet in Treatment C2. Drug: Odalasvir 75 mg Part 2: ODV 75 mg taken orally as a component of FDC tablet (2 tablets of 37.5 mg each) in Treatment G. Drug: AL-335 800 mg Part 1: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A, B, D and E and as a single agent tablet in Treatment C. Part 2: AL-335 800 mg taken orally as a component of FDC tablet in Treatment A2, F (2 tablets of 400 mg each), and G (2 tablets of 400 mg each) and as a single agent tablet in Treatment C2.

Outcome Measures

Primary Outcome Measures

Part 1: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV) [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: Maximum Observed Plasma Concentration (Cmax) of SMV [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: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of SMV [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 the Last Quantifiable (AUC [0-last]) of SMV [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 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV [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 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV [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) [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 2: Maximum Observed Plasma Concentration (Cmax) of ODV [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 the Last Quantifiable (AUC [0-last]) of ODV [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 the Last Quantifiable (AUC [0-last]) of ODV [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: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV [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 Infinite Time (AUC [0-infinity]) of ODV [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 1: Maximum Observed Plasma Concentration (Cmax) of AL-335 [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 2: Maximum Observed Plasma Concentration (Cmax) of AL-335 [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 the Last Quantifiable (AUC [0-last]) of AL-335 [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 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of AL-335 [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: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335 [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 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335 [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 Lansoprazole [Day 5 (1 hour post dose)]
Analyte Concentration at 1 Hour Post Dosing (C1h) of Lansoprazole
Part 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole [Day 5 (2 hour post dose)]
Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole.
Part 1: Analyte Concentration at 1 Hour Post Dosing (C1h) of Omeprazole (if applicable) [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 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Omeprazole (if applicable) [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 Outcome Measures

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]
Exposure will be measured by AUC.
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)]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, irrespective of a causal relationship with the investigational product.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion	Tempe	Arizona	United States	85283

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Research & Development, LLC

ClinicalTrials.gov Identifier:

NCT03059303

Other Study ID Numbers:

CR108273
64294178HPC1018

First Posted:

Feb 23, 2017

Last Update Posted:

Dec 22, 2017

Last Verified:

Dec 1, 2017

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 22, 2017