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

NCT03010059 | Completed Phase 1

• 3 other identifiers: CR1082512016-004018-8664041575RSV1005
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (12)

• Time to Reach Maximum Concentration (Tmax) ALS-008112 (JNJ-63549109)

  Up to Day 8

• Apparent Terminal Elimination Rate Constant (lambda z) of ALS-008112 (JNJ-63549109)

  Up to Day 8

• Apparent Terminal Elimination Half-life (t1/2term) of ALS-008112 (JNJ-63549109)

  Up to Day 8

• Maximum Observed Plasma Concentration (Cmax) of ALS-008144 (JNJ-64167896)

  Up to Day 8

• Time to Reach Maximum Concentration (Tmax) of ALS-008144 (JNJ-64167896)

  Up to Day 8

Study Arms (12)

Panel 1: Treatment ABC

EXPERIMENTAL

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)

Panel 1: Treatment BCA

EXPERIMENTAL

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)

Panel 1: Treatment CAB

EXPERIMENTAL

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)

Panel 1: Treatment ACB

EXPERIMENTAL

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)

Panel 1: Treatment BAC

EXPERIMENTAL

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)

Panel 1: Treatment CBA

EXPERIMENTAL

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)

Panel 2: Treatment DEF

EXPERIMENTAL

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 )

Panel 2: Treatment EFD

EXPERIMENTAL

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 )

Panel 2: Treatment FDE

EXPERIMENTAL

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 )

Panel 2: Treatment DFE

EXPERIMENTAL

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 )

Panel 2: Treatment EDF

EXPERIMENTAL

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 )

Panel 2: Treatment FED

EXPERIMENTAL

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 )

Interventions

JNJ-64041575 (oral suspension formulation) DRUG

Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.

Also known as: ALS-008176

Panel 1: Treatment ABC; Panel 1: Treatment ACB; Panel 1: Treatment BAC; Panel 1: Treatment BCA; Panel 1: Treatment CAB; Panel 1: Treatment CBA

JNJ-64041575 (oral tablet formulation ) DRUG

Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.

Also known as: ALS-008176

Panel 2: Treatment DEF; Panel 2: Treatment DFE; Panel 2: Treatment EDF; Panel 2: Treatment EFD; Panel 2: Treatment FDE; Panel 2: Treatment FED

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) 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 4, 2017
• Study Start: February 6, 2017
• Primary Completion: May 29, 2017
• Study Completion: May 29, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

BE (1)