A Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Erdafitinib

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Erdafitinib

The primary purpose of the study is to characterize the single dose pharmacokinetic of erdafitinib in participants with impaired hepatic function relative to participants with normal hepatic function.

Study Overview

• Status: Terminated
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Erdafitinib

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • CRS Clinical Research Services Kiel GmbH
  • Munchen, Germany, 81241
    • APEX GmbH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Man or woman must have a clinically stable hepatic function as confirmed by the serum bilirubin and transaminase levels measured during screening and those measured on Day -1
• If a woman (a) must not be of childbearing potential postmenopausal or surgically sterile (b) must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the study drug administration
• If a woman who is considered surgically sterile but not postmenopausal, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening (exemptions: pregnancy test not required in female participants with prior hysterectomy or prior bilateral oophorectomy)
• If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the study drug administration
• Participants with hepatic impairment must meet the Child-pug classification for mild, moderate or severe hepatic impairment and must have stable hepatic function

Exclusion Criteria:

• History or current evidence of ophthalmic disorder, such as central serous retinopathy (CSR) or retinal vein occlusion, active wet age related macular degeneration, diabetic retinopathy with macular edema, uncontrolled glaucoma, corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
• Any surgical or medical condition that may alter the absorption, metabolism, or excretion of the study drug (example, gastrectomy, Crohn's disease etc), with the exception of hepatic impairment
• History of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 6 months before screening or positive test result(s) for drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, hallucinogens, and benzodiazepines) at screening and on Day -1
• Known allergy to the study drug or any of the excipients of the formulation (Physical Description of Study Drug[s], for a list of excipients)
• Donated blood or blood products or had substantial loss of blood (more than 500 milliliter [mL]) within 3 months before study drug administration or intention to donate blood or blood products during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Normal Hepatic Function; Participants with normal hepatic function will receive 6 milligram (mg) erdafitinib as a single oral dose under fasted conditions on Day 1.	Drug: Erdafitinib; Participants will receive 6 mg (2*3 mg tablet) erdafitinib as a single oral dose on Day 1. Participants in Cohort 4 may receive a lower dose if warranted by preliminary safety and PK data from Cohorts 2 and 3.; Other Names: JNJ-42756493
Experimental: Cohort 2: Mild Hepatic Impairment; Participants with mild hepatic impairment (Child-Pugh score of 5 or 6) will receive 6 mg erdafitinib as a single oral dose under fasted conditions on Day 1.	Drug: Erdafitinib; Participants will receive 6 mg (2*3 mg tablet) erdafitinib as a single oral dose on Day 1. Participants in Cohort 4 may receive a lower dose if warranted by preliminary safety and PK data from Cohorts 2 and 3.; Other Names: JNJ-42756493
Experimental: Cohort 3: Moderate Hepatic Impairment; Participants with moderate hepatic impairment (Child-Pugh score of 7 to 9) will receive 6 mg erdafitinib as a single oral dose under fasted conditions on Day 1.	Drug: Erdafitinib; Participants will receive 6 mg (2*3 mg tablet) erdafitinib as a single oral dose on Day 1. Participants in Cohort 4 may receive a lower dose if warranted by preliminary safety and PK data from Cohorts 2 and 3.; Other Names: JNJ-42756493
Experimental: Cohort 4: Severe Hepatic Impairment; Participants with severe hepatic impairment (Child-Pugh score of 10 to 15) will only be enrolled to receive appropriate dose level of erdafitinib after review of preliminary safety and pharmacokinetic (PK) data from the mild and moderate hepatic impairment cohorts.	Drug: Erdafitinib; Participants will receive 6 mg (2*3 mg tablet) erdafitinib as a single oral dose on Day 1. Participants in Cohort 4 may receive a lower dose if warranted by preliminary safety and PK data from Cohorts 2 and 3.; Other Names: JNJ-42756493

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax is the maximum observed plasma concentration.	Up to 21 days
Time to Reach the Maximum Observed Plasma Concentration (Tmax)	Tmax is the time to reach maximum observed plasma concentration.	Up to 21 days
Area Under Plasma Concentration-Time Curve (AUC)	AUC is area under plasma concentration-time curve.	Up to 21 days
Terminal Elimination Half-life (t1/2term, Lambda)	t1/2term, Lambda is elimination half-life associated with the terminal slope (Lambda[Z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda(Z).	Up to 21 days
Total Plasma Clearance (CL/F)	CL/F is total plasma clearance of drug after extravascular administration, uncorrected for absolute bioavailability (BA), calculated as Dose/AUC (0-infinity).	Up to 21 days
Apparent Volume of Distribution (Vd/F)	Vd/F is apparent volume of distribution after extravascular administration, uncorrected for absolute BA.	Up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily have a causal relationship with the relevant investigational product.	Approximately 50 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2018
• Primary Completion (Actual): December 22, 2020
• Study Completion (Actual): December 22, 2020

Study Registration Dates

• First Submitted: July 4, 2018
• First Submitted That Met QC Criteria: July 4, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CR108483; 2018-001104-11 (EudraCT Number); 42756493EDI1008 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

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