Healthy
Conditions
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.
Interventions
DRUGSimeprevir 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.
DRUGOdalasvir 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.
DRUGOdalasvir 12.5 mg
Part 1: ODV 12.5 mg taken orally as a component of FDC tablet in Treatment B.
DRUGOdalasvir 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.
DRUGAL-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.
DRUGLansoprazole 30 mg
30 mg lansoprazole once daily from Day 1 to Day 5.
DRUGOmeprazole 20 mg
20 mg omeprazole once daily from Day 1 to Day 5.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 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: 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Outcome results
None listed