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)

Janssen (J&J Innovative Medicine)

Status and phase: Terminated; Phase 1

Conditions: Healthy

Treatments: Drug: Odalasvir 12.5 mg; Drug: Lansoprazole 30 mg; Drug: Simeprevir 75 mg; Drug: Odalasvir 75 mg; Drug: Odalasvir 25 mg; Drug: AL-335 800 mg; Drug: Omeprazole 20 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03059303

CR108273

64294178HPC1018 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 72 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 13 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

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

Experimental group

Description:

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.

Treatment:

Drug: Odalasvir 12.5 mg

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

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

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

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

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Drug: Lansoprazole 30 mg

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

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Drug: Omeprazole 20 mg

Part 2: Treatment Sequence A2-F

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence F-A2

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence C2-F

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence F-C2

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence C2-G

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence G-C2

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence F-G

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 75 mg

Drug: Odalasvir 25 mg

Part 2: Treatment Sequence G-F

Experimental group

Description:

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.

Treatment:

Drug: AL-335 800 mg

Drug: Simeprevir 75 mg

Drug: Odalasvir 75 mg

Drug: Odalasvir 25 mg