A Study to Assess the Relative Bioavailability of 7 Test Tablet Formulations of JNJ-56021927 With Respect to the Capsule Formulation of JNJ-56021927 in Healthy Male Participants

A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Relative Bioavailability of 7 Test Tablet Formulations of JNJ-56021927 With Respect to the Capsule Formulation of JNJ-56021927 Under Fasted Conditions in Healthy Male Subjects

The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication) and relative bioavailability (the extent to which a medication or other substance becomes available to the body) of JNJ-56021927 when administered as 7 test tablet formulations of JNJ-56021927 compared with the softgel capsule formulation of JNJ-56021927 in healthy male participants under fasted conditions at a single dose of 240 mg.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-56021927 capsule; Drug: JNJ-56021927 tablet

Detailed Description

This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), single-center, 8-treatment, parallel-group (each group of participants will be treated at the same time) study. Approximately 120 participants (15 participants in each treatment group) will participate in this study. All participants will be randomly assigned to 1 of 8 possible treatments (A, B, C, D, E, F, G, and H). The study will consist of a screening phase (within 21 days before the first administration of the study medication), a treatment phase with 8 parallel single-dose treatments (8 days); a follow up phase (42 days) and an end-of-study or early withdrawal assessments (Day 57). Safety will be evaluated by the assessment of adverse events, clinical laboratory tests, vital signs, and physical examination which will be monitored throughout the study. The duration of participation in the study for an individual participant will be approximately 78 days.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• During the study and for 3 months after receiving study medication, must agree to use an adequate contraception method (eg, vasectomy, double-barrier, partner using effective contraception), always use a condom during sexual intercourse and to not donate sperm
• Body mass index (weight [kg]/height [m]2) between 18 and 30 kg/m2 and body weight not less than 50 kg
• Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
• A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function
• Non-smoker for 2 months prior to study participation

Exclusion Criteria:

• History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease (including bronchospastic respiratory disease), diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, and infection
• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis, physical examination, vital signs or 12-lead ECG at screening or at admission to the study center as deemed appropriate by the investigator
• Presence of sexual dysfunction (eg, abnormal libido or erectile dysfunction) or any medical condition that would affect sexual function
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for acetaminophen within 14 days before the first dose of the study drug is scheduled
• History of clinically significant allergies or known hypersensitivity to vitamin E

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; 15 participants will receive 240-mg dose as Softgel Capsule Formulation of JNJ-56021927.	Drug: JNJ-56021927 capsule; Participants will receive oral soft gel capsules providing a total dose of 240 mg JNJ-56021927 on Day 1.; Other Names: ARN-509
Experimental: Treatment B; 15 participants will receive 240-mg dose as Tablet Formulation number 1 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment C; 15 participants will receive 240-mg dose as Tablet Formulation number 2 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment D; 15 participants will receive 240-mg dose as Tablet Formulation number 3 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment E; 15 participants will receive 240-mg dose as Tablet Formulation number 4 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment F; 15 participants will receive 240-mg dose as Tablet Formulation number 5 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment G; 15 participants will receive 240-mg dose as Tablet Formulation number 6 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.
Experimental: Treatment H; 15 participants will receive 240-mg dose as Tablet Formulation number 7 of JNJ-56021927.	Drug: JNJ-56021927 tablet; Participants will receive oral tablets providing a total dose of 240 mg JNJ-56021927 on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of JNJ-56021927	The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-56021927	Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Area Under the Plasma Concentration-Time Curve From Time of Administration to 72 hours After Dosing (AUC 0-72h) of JNJ-56021927	The AUC 0-72h is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Area Under the Plasma Concentration-Time Curve From Time of Administration to 168 hours After Dosing (AUC 0-168h) of JNJ-56021927	The AUC 0-168h is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUClast) of JNJ-56021927	The AUClast is area under the plasma concentration-time curve from time zero to the last quantifiable concentration.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of JNJ-56021927	The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of Area under Curve (AUC) last and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration and lambda[z] is the terminal rate-constant of the semi logarithmic drug concentration-time curve.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Elimination Half-Life Period (T1/2) of JNJ-56021927	The Elimination Half-Life Period (T1/2) is the time measured for the plasma concentration to decrease by 1 half of its original concentration. It is associated with the terminal rate-constant (lambda[z]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
First-order Rate Constant of JNJ-56021927	The 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, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Time to Last Quantifiable Plasma Concentration (tlast) of JNJ-56021927		Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Relative Bioavailability (Frel) of JNJ-56021927	Relative bioavailability is the percentage of the administered dose that is systemically available.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Metabolite to Parent Drug Ratio for Cmax of JNJ-56021927	Metabolite to parent drug ratio for maximum observed plasma concentration.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Metabolite to Parent Drug Ratio for AUClast of JNJ-56021927	Metabolite to parent drug ratio for area under the plasma concentration time curve from time 0 to time of the last observed quantifiable concentration (Clast).	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Metabolite to Parent Drug Ratio for AUCinfinity of JNJ-56021927	Metabolite to parent drug ratio for area under the plasma concentration time curve from time 0 to infinite time, calculated as the sum of AUClast and Clast/ first-order rate constant, in which Clast is the last observed quantifiable concentration.	Pre-dose, and post-dose Day 1 (0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours), Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 36, 43, 50, 57
Number of Participants With Adverse Events as a Measure of Safety and Tolerabilty		Up to Day 57

Collaborators and Investigators

• Sponsor: Aragon Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 7, 2014
• First Posted (Estimate): January 9, 2014

Study Record Updates

• Last Update Posted (Estimate): October 20, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Healthy; Bioavailability; ARN-509; JNJ-56021927
• Other Study ID Numbers: CR103299; 56021927PCR1007 (Other Identifier: Janssen Research & Development, LLC)