A Study to Assess the Relative Bioavailability of JNJ64041575 Administered as 2 Different New Concept Formulations (Oral Suspension and Tablet) Compared to Their Respective Current Formulations, and to Assess the Effect of Food on the Pharmacokinetics of the 2 New Concept Formulations

Study Overview
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Brief Summary
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The purpose of this study is to assess the rate and extent of absorption of JNJ-64041575 by measuring ALS-008112 plasma concentrations following administration of a single oral dose of JNJ-64041575 given as 2 new concept formulations (oral suspension and tablet) compared to their respective current formulations under fasted conditions and to assess the effect of food on the pharmacokinetics of the 2 new concept formulations under fed condition in healthy adult participants.

Official Title
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An Open-label, Randomized, 3-way Crossover Study in Healthy Adult Subjects to Assess the Relative Bioavailability of a Single Dose of JNJ-64041575 Administered as 2 Different New Concept Formulations (Oral Suspension and Tablet) Compared to Their Respective Current Formulations, and to Assess the Effect of Food on the Pharmacokinetics of the 2 New Concept Formulations

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-64041575 (oral suspension formulation)
* Drug: JNJ-64041575 (oral tablet formulation )


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter kg/m^2, extremes included, and a body weight not less than 50.0 kg, extremes included Participant must have a normal 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at screening, including: a) normal sinus rhythm (heart rate between 45 and 100 beats per minute [bpm], extremes included); b) QT corrected according to Fridericia's formula (QTcF) interval less than or equal to (<=)430 milliseconds (ms) for male participants and <=450 ms for female participants; c) QRS interval <=110 ms; d) PR interval <=200 ms; e) ECG morphology consistent with healthy cardiac conduction and function. Any evidence of heart block, or of left or right bundle branch block is exclusionary Participants must have normal values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (less than or equal (<=)1.0×upper limit of laboratory normal range [ULN]) Contraceptive use by female participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Before randomization, a woman must be either: a) Not of childbearing potential defined as: 1) Postmenopausal: A postmenopausal state is defined as greater than (>)45 years and no menses for 12 consecutive months without an alternative medical cause and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (>40 International units per liter [IU/L] or milli-international units per milliliter [mIU/mL]), OR; 2) Permanently sterile: Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy b) Of childbearing potential and, if heterosexually active, 1) Practicing a highly effective method of contraception (failure rate of less than (<)1percent (%) per year when used consistently and correctly) 2) Agrees to remain on a highly effective method throughout the study and for at least 44 days after the last dose of study drug A female participant, except if postmenopausal, must have a negative serum beta human chorionic gonadotropin (beta- hCG) pregnancy test at screening, and a negative urine pregnancy test on Day 1 in each treatment period Participant must be able to taste and smell normally, to their own opinion. Participants who have an impaired sense of taste and/or smell due to any conditions such as allergic rhinitis, common cold, or sinusitis are not eligible to take part in the study Exclusion Criteria: Participant has a mouth pathology including, but not limited to, pain, ulcer, edema, mucosal erosion, gingivitis and/or (dental) abscesses, or receives treatment for oral pathologies (eg, antifungals or antibiotics) or oral treatment for any disease Participant with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs Participant is hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive with HCV RNA positive, or has another clinically active liver disease at screening Participant has a history of human immunodeficiency virus type 1 (HIV-1) or HIV 2 antibody positive, or tests positive for HIV-1 or -2 at screening Participant has previously been dosed with JNJ-64041575 in more than 3 single-dose studies with JNJ-64041575 or has previously been dosed with JNJ-64041575 in a multiple-dose study with JNJ-64041575 Participants with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table a) Serum creatinine grade 1 or greater (greater [>]1.0* upper limit of laboratory normal range [ULN]) b) Hemoglobin grade 1 or greater (<=10.5 gram per decilitre [g/dL]) c) Platelet count grade 1 or greater (<=99.999/millimeter [mm]^3) d) Reticulocyte count (absolute) below the lower limit of laboratory normal range (LLN) e) Absolute neutrophil count grade 1 or greater (<=1,500/mm^3) f) Total bilirubin grade 1 or greater (>1.0*ULN) g) Any other toxicity grade 2 or above, except for grade 2 elevations of low density lipoprotein (LDL) cholesterol and/or cholesterol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel 1: Treatment ABC<br>Participants will receive 240 milligram (mg) JNJ-64041575 as 6.0 milliliter (mL) of a 40-milligram per milliliter (mg/mL) current oral suspension formulation (reference 1) under fasted conditions (Treatment A) in period 1, then 4.0 mL of a 60-mg/mL new concept oral suspension formulation (test 1) under fasted conditions (Treatment B) in period 2 followed by 4.0 mL of a 60-mg/mL new concept oral suspension formulation (test 2) under fed conditions (Treatment C) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 1: Treatment BCA<br>Participants will receive Treatment B (test 1) in period 1, then Treatment C (test 2) in period 2 followed by Treatment A (reference 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 1: Treatment CAB<br>Participants will receive Treatment C (test 2) in period 1, then Treatment A (reference 1) in period 2 followed by Treatment B (test 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 1: Treatment ACB<br>Participants will receive Treatment A (reference 1) in period 1, then Treatment C (test 2) in period 2 followed by Treatment B (test 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 1: Treatment BAC<br>Participants will receive Treatment B (test 1) in period 1, then Treatment A (reference 1) in period 2 followed by Treatment C (test 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 1: Treatment CBA<br>Participants will receive Treatment C (test 2) in period 1, then Treatment B (test 1) in period 2 followed by Treatment A (reference 1) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral suspension formulation)<br>* Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment DEF<br>Participants will receive JNJ-64041575 as 1 tablet of the 250-mg current oral tablet formulation (reference 2) under fasted conditions (Treatment D) in period 1, then 1 tablet of the 250-mg new concept oral tablet formulation (test 3) under fasted conditions (Treatment E) in period 2 followed by 1 tablet of the 250-mg new concept oral tablet formulation (test 4) under fed conditions (Treatment F) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment EFD<br>Participants will receive Treatment E (test 3) in period 1, then Treatment F (test 4) in period 2 followed by Treatment D (reference 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment FDE<br>Participants will receive Treatment F (test 4) in period 1, then Treatment D (reference 2) in period 2 followed by Treatment E (test 3) then in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment DFE<br>Participants will receive Treatment D (reference 2) in period 1, then Treatment F (test 4) in period 2 followed by Treatment E (test 3) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment EDF<br>Participants will receive Treatment E (test 3) in period 1, then Treatment D (reference 2) in period 2 followed by Treatment F (test 4) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|
| Experimental: Panel 2: Treatment FED<br>Participants will receive Treatment F (test 4) in period 1, then Treatment E (test 3) in period 2 followed by Treatment D (reference 2) in period 3 on Day 1. There will be a washout period of at least 14 days between study drug intake in subsequent treatment periods. | Drug: JNJ-64041575 (oral tablet formulation )<br>* Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.<br>* Other names: ALS-008176;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of ALS-008112 (JNJ-63549109) | Cmax is the maximum observed plasma concentration. | Up to Day 8 | 
| Area Under Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) of ALS-008112 (JNJ-63549109) | 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. | Up to Day 8 | 
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ALS-008112 (JNJ-63549109) | 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. | Up to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Concentration (Tmax) ALS-008112 (JNJ-63549109) | Tmax is defined as actual sampling time to reach maximum observed plasma concentration. | Up to Day 8 | 
| Apparent Terminal Elimination Rate Constant (lambda z) of ALS-008112 (JNJ-63549109) | Apparent terminal elimination rate constant, determined by linear regression using the terminal log linear phase of the log transformed concentration versus time curve. | Up to Day 8 | 
| Apparent Terminal Elimination Half-life (t1/2term) of ALS-008112 (JNJ-63549109) | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration time curve and calculated as 0.693/apparent terminal elimination rate constant (lambda[z]). | Up to Day 8 | 
| Maximum Observed Plasma Concentration (Cmax) of ALS-008144 (JNJ-64167896) | Cmax is the maximum observed plasma concentration. | Up to Day 8 | 
| Time to Reach Maximum Concentration (Tmax) of ALS-008144 (JNJ-64167896) | Tmax defined as the actual sampling time to reach the maximum observed plasma concentration. | Up to Day 8 | 
| Area Under Plasma Concentration Curve from time zero to the last quantifiable (AUC [0-last]) of ALS-008144 (JNJ-64167896) | AUC (0-last) defined as 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. | Up to Day 8 | 
| Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ALS-008144 (JNJ-64167896) | 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. | Up to Day 8 | 
| Apparent Terminal Elimination Rate Constant (lambda z) of ALS-008144 (JNJ-64167896) | Apparent terminal elimination rate constant, determined by linear regression using the terminal log linear phase of the log transformed concentration versus time curve. | Up to Day 8 | 
| Apparent Terminal Elimination Half-life (t1/2term) of ALS-008144 (JNJ-64167896) | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration time curve and calculated as 0.693/apparent terminal elimination rate constant (lambda[z]). | Up to Day 8 | 
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Safety and Tolerability | Screening (28 days ) to Follow up Phase (10 to 14 days after last dose) | 
| Taste of JNJ-64041575 following administration of different oral suspension formulations under fed and fasted conditions in healthy adult participants in Panel 1 (taste questionnaire) | Participants will complete a taste questionnaire within 5 to 15 minutes after study drug intake in each treatment period. For the taste questionnaire, a dichotomization will be made for the overall question, categorizing 'bad' and 'almost acceptable' versus 'acceptable' and 'good'. | Day 1 | 
| Taste and Swallowability of JNJ-64041575 following administration of different oral tablet formulations under fed and fasted conditions in healthy adult participants in Panel 2 (taste and swallowability questionnaire) | A taste and swallowability questionnaire will be completed by the participant within 5 to 15 minutes after each study drug intake in each treatment period, to compare the taste and swallowability (tablets only) of JNJ-64041575 following administration of different oral formulations under fed and fasted conditions. For the taste questionnaire, a dichotomization will be made for the overall question, categorizing 'bad' and 'almost acceptable' versus 'acceptable' and 'good'. For the swallowability, a dichotomization will be made of 'slightly difficult' or worse versus 'neither difficult nor easy' or better. The results of the questionnaire will be transcribed into the e-Source by a member of the study-site personnel. | Day 1 |