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)

NCT03059303 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CR10827364294178HPC1018
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (22)

• Part 1: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 2: Maximum Observed Plasma Concentration (Cmax) of SMV

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of SMV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of SMV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of SMV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post-dose

• Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose

• Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of ODV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of ODV

  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.

  Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV

  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.

  Predose, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, 312 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV

  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.

  Predose, 1, 2, 4, 6, 7, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 288, and 312 hours post-dose

• Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-335

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-335

  Cmax is defined as the maximum observed plasma concentration.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of AL-335

  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.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of AL-335

  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.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335

  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.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335

  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.

  Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose

• Part 1: Analyte Concentration at 1 Hour Post Dosing (C1h) of Lansoprazole

  Analyte Concentration at 1 Hour Post Dosing (C1h) of Lansoprazole

  Day 5 (1 hour post dose)

• Part 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole

  Analyte Concentration at 2 Hour Post Dosing (C2h) of Lansoprazole.

  Day 5 (2 hour post dose)

• Part 1: Analyte Concentration at 1 Hour Post Dosing (C1h) of Omeprazole (if applicable)

  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).

  Day 5 (1 hour post dose)

• Part 1: Analyte Concentration at 2 Hour Post Dosing (C2h) of Omeprazole (if applicable)

  Analyte concentration will only be assessed if participants receive omeprazole (only in case an DDI is observed for participants who received lansoprazole).

  Day 5 (2 hour post dose)

Secondary Outcomes (2)

• 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)

Study Arms (13)

Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]

EXPERIMENTAL

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; Drug: Odalasvir 12.5 mg; Drug: AL-335 800 mg

Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg; Drug: Lansoprazole 30 mg

Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg; Drug: Omeprazole 20 mg

Part 2: Treatment Sequence A2-F

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence F-A2

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence C2-F

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence F-C2

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence C2-G

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: Odalasvir 75 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence G-C2

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: Odalasvir 75 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence F-G

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: Odalasvir 75 mg; Drug: AL-335 800 mg

Part 2: Treatment Sequence G-F

EXPERIMENTAL

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; Drug: Odalasvir 25 mg; Drug: Odalasvir 75 mg; Drug: AL-335 800 mg

Interventions

Simeprevir 75 mg DRUG

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.

Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]; Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]; Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335; Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]; Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]; Part 2: Treatment Sequence A2-F; Part 2: Treatment Sequence C2-F; Part 2: Treatment Sequence C2-G; Part 2: Treatment Sequence F-A2; Part 2: Treatment Sequence F-C2; Part 2: Treatment Sequence F-G; Part 2: Treatment Sequence G-C2; Part 2: Treatment Sequence G-F

Odalasvir 25 mg DRUG

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.

Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]; Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335; Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]; Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]; Part 2: Treatment Sequence A2-F; Part 2: Treatment Sequence C2-F; Part 2: Treatment Sequence C2-G; Part 2: Treatment Sequence F-A2; Part 2: Treatment Sequence F-C2; Part 2: Treatment Sequence F-G; Part 2: Treatment Sequence G-C2; Part 2: Treatment Sequence G-F

Odalasvir 12.5 mg DRUG

Part 1: ODV 12.5 mg taken orally as a component of FDC tablet in Treatment B.

Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]

Odalasvir 75 mg DRUG

Part 2: ODV 75 mg taken orally as a component of FDC tablet (2 tablets of 37.5 mg each) in Treatment G.

Part 2: Treatment Sequence C2-G; Part 2: Treatment Sequence F-G; Part 2: Treatment Sequence G-C2; Part 2: Treatment Sequence G-F

AL-335 800 mg DRUG

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.

Part 1: Treatment A: FDC [SMV(75mg)+ODV(25mg)+AL-335(800mg)]; Part 1: Treatment B: FDC [SMV(75mg)+ODV(12.5mg)+AL-335(800mg)]; Part 1: Treatment C: Simeprevir, Odalasvir, and AL-335; Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]; Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]; Part 2: Treatment Sequence A2-F; Part 2: Treatment Sequence C2-F; Part 2: Treatment Sequence C2-G; Part 2: Treatment Sequence F-A2; Part 2: Treatment Sequence F-C2; Part 2: Treatment Sequence F-G; Part 2: Treatment Sequence G-C2; Part 2: Treatment Sequence G-F

Lansoprazole 30 mg DRUG

30 mg lansoprazole once daily from Day 1 to Day 5.

Also known as: Prevacid

Part 1: Treatment D: Lansoprazole + FDC [SMV+ODV+AL-335]

Omeprazole 20 mg DRUG

20 mg omeprazole once daily from Day 1 to Day 5.

Part 1: Treatment E: Omeprazole + FDC [SMV+ODV+AL-335]

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Female participant must have a negative highly sensitive urine or serum pregnancy test at Day -1

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Simeprevir; odalasvir; adafosbuvir; Lansoprazole; Omeprazole

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles; Heterocyclic Compounds, 2-Ring

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: February 20, 2017
• Primary Completion: April 24, 2017
• Study Completion: April 24, 2017
• Last Updated: December 22, 2017

Record last verified: 2017-12

Locations

US (1)