A Study of Steady-state Carbamazepine on the Single-dose of Erdafitinib Tablets in Healthy Adult Participants

An Open-label, Single-sequence, Drug-drug Interaction Study to Evaluate the Effect of Steady-state Carbamazepine on the Single-dose Pharmacokinetics of Erdafitinib Tablets in Healthy Adult Subjects

The main purpose of this study is to evaluate the effect of multiple doses of carbamazepine (a strong inducer of cytochrome P450 [CYP]3A4 and a weak inducer of CYP2C9) on the pharmacokinetics of a single oral dose of erdafitinib in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Erdafitinib; Drug: Carbamazepine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy on the basis of physical examination, medical history, and vital signs (blood pressure, pulse, and body temperature) performed at screening
• Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel and hematology panel are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator. Participants must have sodium and phosphate levels within normal limits; hematological parameters (Hemoglobin, red blood cell [RBC] count, white blood cell [WBC] count, absolute neutrophil count, platelet count) within normal limits; and total bilirubin, alanine aminotransferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) serum levels lower than or equal to the upper limit of normal at screening
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Must agree to have a pharmacogenomic blood sample (5 milliliters [mL]) collected at screening to allow for pharmacogenomic analysis
• Non-smoker for at least 6 months before first study drug administration

Exclusion Criteria:

• History of depression or suicidal ideation
• 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
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol (a maximum of 3 doses per day of 500 milligram [mg] paracetamol, and no more than 3 gram [g] per week), hormonal replacement therapy and cetirizine (in case of allergic reactions), within 14 days before the first dose of the study drug is scheduled until completion of the study
• Received an experimental drug or used an experimental medical device within 1 month or within a period less than 5 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled
• Known allergies, hypersensitivity, or intolerance to erdafitinib or carbamazepine or any of the excipients of the formulations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Erdafitinib and Carbamazepine; Participants will receive single oral dose of erdafitinib dose 1 on Day 1 30 minutes after the start of a standardized breakfast in Period 1 followed by repeated doses of carbamazepine orally every 12 hours from Days 15 to 35 (carbamazepine Dose 1 from Days 15 to 17, Dose 2 from Days 18 to 20, and then Dose 3 from Days 21 to 35) 30 minutes after the start of standardized meal (breakfast and dinner) in Period 2. After 8 Days of Dose 3 carbamazepine treatment, on Day 28, participants will receive a single oral dose of erdafitinib dose 1 with that day's carbamazepine dose.

Drug: Erdafitinib; Participants will receive single oral dose of erdafitinib tablets on Day 1 in Period 1 and on Day 28 in Period 2.; Other Names: JNJ-42756493; Drug: Carbamazepine; Participants will receive an oral dose of carbamazepine tablets from Day 15 to 35 in Period 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma (Cmax) of Erdafitinib	Cmax is defined as the maximum observed plasma of erdafitinib concentration.	Predose (Day 28) 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 and 312 hours postdose (Day 41)
Area Under the Plasma Analyte Concentration-Time Curve 0 from Time 0 to one week Postdose (AUC[0-168 hours])	AUC (0-168 hours) is defined as the area under the plasma analyte concentration-time curve from time 0 to one week postdose (168 hours).	Predose (Day 28) 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 168 hours postdose (Day 35)
Area Under the Plasma Analyte Concentration-Time Curve from Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last])	AUC (0-last) is defined as area under the plasma analyte concentration-time curve from time 0 to time of the last observed quantifiable concentration.	Predose (Day 28) 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 and 312 hours postdose (Day 41)
Area Under the Analyte Concentration-Time Curve from Time 0 to Infinite Time (AUC [0-infinity])	AUC (0-infinity) is defined as the area under the analyte concentration-time curve from time 0 to infinite time.	Predose (Day 28) 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 and 312 hours postdose (Day 41)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability	An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to Day 79 (end of study)

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Investigators: Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Actual): June 14, 2022
• Study Completion (Actual): June 14, 2022

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Carbamazepine
• Other Study ID Numbers: CR108763; 2019-003473-26 (EudraCT Number); 42756493NAP1001 (Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

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