A Crossover Study to Evaluate Relative Bioavailability of Two JNJ-54781532 Tablet Formulations in Healthy Adult Participants

A Single-Dose, Open-Label, Randomized, Crossover Study to Assess the Relative Bioavailability of Two JNJ-54781532 Tablet Formulations Under Fed Conditions in Healthy Adult Subjects

The purpose of this study is to evaluate the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of JNJ-54781532 formulation 2 (test) compared with JNJ-54781532 formulation 1 (reference) in healthy participants under fed conditions at a single dose of 150 milligram (mg).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Formulation 2; Drug: Formulation 1

Detailed Description

This is a randomized (study medication assigned to participants by chance), open-label (all people know the identity of the intervention), 2-treatment, 2-period, 2-sequence crossover (participants may receive different interventions sequentially during the trial), and single-center study of JNJ-54781532. The duration of study will be approximately of 5 weeks per participant. The study consists of 3 parts: Screening (that is, 21 days before study commences on Day 1); Open-label Treatment (consists of 2 single-dose treatments, either JNJ-54781532 formulation 1 [reference] or JNJ-54781532 formulation 2 [test]), in subsequent 2-treatment periods, each separated with washout period of 7 days); and End-of-Study (done upon completion of the 72-hour pharmacokinetic sampling on Day 4 of Period 2, or at the time of early withdrawal). All the eligible participants will be randomly assigned to 1 of the 2 treatment sequences to ensure that they receive both of the following treatments, one in each period. Followed by an overnight fast of at least 10 hours participants will be administered with study treatment 30 minutes after high-fat, high-calorie breakfast. Participants will not be allowed to have food until 4 hours of drug administration. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of two formulations of JNJ-54781532 (test and reference) will be evaluated primarily. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female participants must be either: 1) not of childbearing potential: postmenopausal or surgically sterile at screening 2) of child-bearing potential: Must use highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening, and agree to use highly effective contraception throughout the study period, and for 90 days after final study drug administration. Women, who are not heterosexually active at Screening, must agree to utilize a highly-effective method of birth control if they become heterosexually active during their participation in the study
• Must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test on Day (-)1 of Period 1
• Female participants must agree not to donate ova starting at screening and throughout the study period, and for 90 days after the final study drug administration
• If a man who is sexually active with a woman of child-bearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator (for example, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 90 days after receiving the last dose of study drug
• Participants eligible according to the following tuberculosis (TB) screening criteria: 1) following tuberculosis (TB) screening criteria 2) have no signs or symptoms suggestive of active TB upon medical history and/or physical examination 3) have had no recent close contact with a person with active TB 4. Within 2 months prior to the first administration of study agent, have a negative T-spot or QuantiFERON-TB Gold test result

Exclusion Criteria:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection
• Participant had major gastrointestinal (GI) surgery
• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or at admission to the study center on Day (-) 1 of Period 1
• Participant has an aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than or equal to (>=) the upper limit of normal (ULN)
• History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) criteria within 1 year before Screening or positive test result(s) for alcohol and/or drugs of abuse (such as barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at screening or Day (-) 1 of Period 1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (Formulation 2 Then Formulation 1); Single-dose of JNJ-54781532 formulation 2 will be administered as 150 milligram (mg) oral tablet in first treatment period; followed by JNJ-54781532 formulation 1 as 150 mg orally (5*30 mg tablet=150 mg) in second treatment period. A washout period of at least 7 days will be maintained between each treatment period.	Drug: Formulation 2; Single-dose of JNJ-54781532 formulation 2 will be administered as 150 milligram (mg) oral tablet in one of the treatment periods.; Other Names: JNJ-54781532 Test; Drug: Formulation 1; Single-dose of JNJ-54781532 formulation 1 will be administered as 150 milligram (mg) oral tablet (5*30 mg tablet=150 mg) in one of the treatment periods.; Other Names: JNJ-54781532 Reference
Experimental: Group 2 (Formulation 1 Then Formulation 2); Single-dose of JNJ-54781532 formulation 1 will be administered as 150 mg oral tablet (5*30 mg tablet=150 mg) in first treatment period; followed by JNJ-54781532 formulation 2 as 150 mg oral tablet in second treatment period. A washout period of at least 7 days will be maintained between each treatment period.	Drug: Formulation 2; Single-dose of JNJ-54781532 formulation 2 will be administered as 150 milligram (mg) oral tablet in one of the treatment periods.; Other Names: JNJ-54781532 Test; Drug: Formulation 1; Single-dose of JNJ-54781532 formulation 1 will be administered as 150 milligram (mg) oral tablet (5*30 mg tablet=150 mg) in one of the treatment periods.; Other Names: JNJ-54781532 Reference

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of JNJ-54781532	The Cmax is the maximum observed plasma concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Time to Reach Maximum Concentration (tmax) of JNJ-54781532	The tmax is time to reach the maximum observed plasma concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of JNJ-54781532	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-54781532	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(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Bioavailability of JNJ-54781532	Bioavailability means the extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Relative bioavailability of single-dose of two formulations of JNJ-54781532 will be compared in healthy participants under fed conditions.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Time to last quantifiable plasma concentration (tlast) of JNJ-54781532	The tlast is the time to last observed quantifiable plasma concentration.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Area Under the Plasma Concentration Percentage (%) Extrapolation of JNJ-54781532	The percentage of AUC (0-infinity) that is due to extrapolation from Tlast to infinity (AUC%Extrapolation) is calculated by using the formula AUC_%extrapolation = 100*(AUC [0-infinity] minus (AUC [0-last])/(AUC (0-infinity).	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Elimination Half-Life (t [1/2] Lambda) of JNJ-54781532	Elimination half-life (t [1/2] Lambda) is associated with the terminal slope (lambda [z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Rate Constant (Lambda[z])	Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1
Adjusted Coefficient of Determination (R^2 adj)	The coefficient of determination adjusted for the number of points used in the estimation of Lambda(z).	Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, and 48 hours (h) post-dose of JNJ-54781532 on Day 1

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 16, 2014
• First Submitted That Met QC Criteria: April 16, 2014
• First Posted (Estimate): April 21, 2014

Study Record Updates

• Last Update Posted (Estimate): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Healthy; Phase 1; Biological Availability; JNJ-39220675
• Other Study ID Numbers: CR104088; 54781532ARA1001