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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03010059
• Other study ID #: CR108251
• Secondary ID: 2016-004018-8664
• Status: Completed
• Phase: Phase 1
• First received: January 3, 2017
• Last updated: June 22, 2017
• Start date: February 6, 2017
• Est. completion date: May 29, 2017

Study information

• Verified date: June 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: May 29, 2017
• Est. primary completion date: May 29, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-64041575 (oral suspension formulation)
Participants will receive 240 mg JNJ-64041575 under fasted and fed conditions in Panel 1 as current/new concept oral suspension formulation.
• JNJ-64041575 (oral tablet formulation )
Participants will receive 250 mg JNJ-64041575 under fasted and fed conditions in Panel 2 as current/new concept oral tablet formulation.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of ALS-008112 (JNJ-63549109)	Cmax is the maximum observed plasma concentration.	Up to Day 8
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Maximum Observed Plasma Concentration (Cmax) of ALS-008144 (JNJ-64167896)	Cmax is the maximum observed plasma concentration.	Up to Day 8
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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