A Study to Evaluate the Pharmacokinetics of JNJ-56021927 in Participants With Mild or Moderate Hepatic Impairment Compared With Participants With Normal Hepatic Function

A Single-Dose, Open-Label Study to Evaluate the Pharmacokinetics of JNJ-56021927 in Subjects With Mild or Moderate Hepatic Impairment Compared With Subjects With Normal Hepatic Function

The purpose of this study is to characterize the pharmacokinetics of JNJ-56021927 in participants with mild and moderate hepatic impairment.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: JNJ-56021927

Detailed Description

This is an open-label (all people know the identity of the intervention), single-dose, single-center, non-randomized study of JNJ-56021927 in participants who either have hepatic impairment or qualify for the control group. The study consists of 3 Phases: Screening Phase (21 Days), open-label treatment Phase (8 Days) and follow up Phase (49 Days). The duration of participation in the study for each participant is approximately 78 Days. Primarily the pharmacokinetics of JNJ-56021927 will be measured. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States
  • Texas
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Must have a clinically stable hepatic function as confirmed by the serum bilirubin and transaminase levels measured during Screening and those measured within 24 hours prior to study drug administration
• Sign an informed consent document indicating that the participant understands the purpose of and procedures required for the study and are willing to participate in the study. Participants must not have hepatic encephalopathy greater than or equal to (>=) Grade 3 where the participant lacks the capacity to provide informed consent as judged by the investigator. Mild or moderate hepatic encephalopathy that would not impede informed consent in the investigator's judgment is permitted
• Willing and able to adhere to the prohibitions and restrictions as specified in the protocol
• If a man is sexually active with a woman of childbearing potential and has not had a vasectomy, he must agree to use an adequate contraception method as deemed appropriate by the Investigator, always use a condom during sexual intercourse, and agree to not donate sperm during the study and for 3 months after receiving the study drug
• Body mass index (BMI) between 18 and 35 kilogram (kg)/meter (m)^2 (inclusive), and body weight not less than 50 kg
• The participant must have a total Child-Pugh score of 5 to 6, inclusive (mild); or 7 to 9, inclusive (moderate); the investigator will determine hepatic impairment

Exclusion Criteria:

• Screening thyroid-stimulating hormone (TSH) level greater than (>) Upper Limit of Normal (ULN), or participants with known history of thyroid disorders
• Participant who is on thyroid replacement therapy
• History of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) criteria within 2 years before Screening or positive test result(s) for drugs of abuse (that is, opiates, barbiturates, benzodiazepines, cocaine, cannabinoids, and amphetamines) at Screening or Day -1. A positive test for participants with prescriptions for drugs that may interfere with the drug screen (that is, opiates and benzodiazepines) may be allowed
• Known allergy to the study drug or any of the excipients of the formulation
• Intention to donate blood or blood products during the study or for 3 months after the administration of the study drug
• A man who plans to father a child while enrolled in the study or for 3 months after receiving the study drug
• Known history of seizure or condition that may predispose to seizure or on medication that lowers seizure threshold
• History of stomach or intestinal surgery or resection that would potentially alter absorption or excretion of orally administered drugs
• Gall bladder (example, cholecystitis and cholelithiasis) or biliary tract disease
• Clinically significant renal laboratory findings including serum creatinine level greater than (>) 1.5 times ULN
• Inability to fast for 12 hours
• History of or current clinically significant medical illness
• Positive test for human immunodeficiency virus (HIV) 1 and 2 antibodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-56021927; Participants with mild and moderate hepatic impairment and with normal hepatic function will receive JNJ-56021927 240 milligram (mg) orally once on Day 1.	Drug: JNJ-56021927; Participants will receive JNJ-56021927 240 milligram (mg) orally once on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of JNJ-56021927	The Cmax is the maximum observed plasma concentration of JNJ-56021927.	Pre-dose up to 1344 hours post-dose
Maximum Plasma Concentration Corrected for Unbound Fraction (Cmax_unb) of JNJ-56021927	The Cmax_unb is the maximum observed plasma concentration corrected for unbound fraction of JNJ-56021927.	Pre-dose up to 1344 hours post-dose
Time to Reach the Maximum Plasma Concentration (Tmax) of JNJ-56021927	The Tmax is the time to reach the maximum observed plasma concentration of JNJ-56021927.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC[0-24]) Post Dose of JNJ-56021927	The AUC(0-24hrs) is the area under the plasma concentration-time curve from 0 to 24 hours post dosing.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to 168 Hours (AUC[0-168]) Post Dose of JNJ-56021927	The AUC(0-168hrs) is the area under the plasma concentration-time curve from 0 to 168 hours post dosing.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration (AUC[0-last]) Post Dose of JNJ-56021927	The AUC(0-last) is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to Last Quantifiable Concentration Corrected for Unbound Fraction (AUC[last_unb]) Post Dose of JNJ-56021927	The AUC(last_unb) corrected for unbound fraction is the area under the plasma concentration-time curve from 0 to time of the last quantifiable concentration.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of JNJ-56021927	The AUC (0-infinity) is the area under the plasma JNJ-56021927 concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma JNJ-56021927 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.	Pre-dose up to 1344 hours post-dose
Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time Corrected for Unbound Fraction (AUC[infinity_unb]) Post Dose of JNJ-56021927	The AUC(infinity_unb) is the area under the plasma JNJ-56021927 concentration-time curve from time 0 to infinite time corrected for unbound fraction, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma JNJ-56021927 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.	Pre-dose up to 1344 hours post-dose
Percentage of Area Under the Plasma Concentration-Time Curve Obtained by Extrapolation (%AUC[infinity,ex])	The %AUC[infinity,ex] is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity) and then multiplying by 100, (AUC[0-infinity] - AUC[0-last])*100/AUC[0-infinity].	Pre-dose up to 1344 hours post-dose
Terminal Half-life (t[1/2]) of JNJ-56021927	Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).	Pre-dose up to 1344 hours post-dose
Elimination Rate Constant (Lambda [z]) of JNJ-56021927	The Lambda (z) determined by 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 up to 1344 hours post-dose
Time of Last Measurable Plasma Concentration (Tlast) of JNJ-56021927	Time to last measurable plasma concentration is evaluated.	Pre-dose up to 1344 hours post-dose
Total Apparent Clearance (CL/F) of JNJ-56021927	The CL/F is defined as Dose/AUC (0-infinity).	Pre-dose up to 1344 hours post-dose
Apparent Volume of Distribution (Vd/F) of JNJ-56021927	The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].	Pre-dose up to 1344 hours post-dose
Metabolite to Parent Drug Ratio for Maximum Observed Plasma Concentration (MPR Cmax)	The (MPR Cmax) is metabolite to parent drug ratio for maximum observed plasma concentration.	Pre-dose up to 1344 hours post-dose
Metabolite to Parent Drug Ratio for Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Quantifiable Concentration (MPR AUC[0-last])	The MPR AUClast is metabolite to parent drug ratio for area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUC [0-last]).	Pre-dose up to 1344 hours post-dose
Metabolite to Parent Drug Ratio for Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (MPR AUC [0-infinity])	The MPR AUC [0-infinity] is metabolite to parent drug ratio for area under the plasma concentration-time curve from time zero to extrapolated infinite time (AUC [0-infinity]).	Pre-dose up to 1344 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) and Serious AEs	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Screening up to follow-up (56 days after dose administration)

Collaborators and Investigators

• Sponsor: Aragon Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• A Single-Dose, Open-Label Study to Evaluate the Pharmacokinetics of JNJ-56021927 in Subjects With Mild or Moderate Hepatic Impairment Compared With Subjects With Normal Hepatic Function

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2015
• Primary Completion (Actual): February 9, 2017
• Study Completion (Actual): February 9, 2017

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 17, 2015

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Hepatic Impairment; JNJ-56021927
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CR107774; 56021927PCR1018 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No