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A Study to Evaluate the Effect of Fluconazole and Itraconazole on Erdafitinib Pharmacokinetics in Healthy Adult Participants

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ClinicalTrials.gov Identifier: NCT03135106
Recruitment Status : Completed
First Posted : May 1, 2017
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the effect of multiple doses of fluconazole (an inhibitor of cytochrome P450 [CYP] 2C9 and CYP3A) and itraconazole (an inhibitor of CYP3A4 and P-glycoprotein [P-gp]) on the pharmacokinetics of a single 4-milligram (mg) oral dose of erdafitinib in healthy adult participants.

Condition or disease Intervention/treatment Phase
Healthy Drug: Erdafitinib Drug: Fluconazole Drug: Itraconazole Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Randomized, Open-Label, Parallel Group, Drug-drug Interaction Study to Evaluate the Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adult Subjects
Actual Study Start Date : April 14, 2017
Actual Primary Completion Date : September 1, 2017
Actual Study Completion Date : September 1, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment A: Erdafitinib alone
Participants will receive single 4 milligram (mg) oral dose of erdafitinib on Day 1 in a fasted state.
Drug: Erdafitinib
A single 4-mg of erdafitinib tablet will be administered on Day 1 in Treatment A and on Day 5 in Treatment B and C.
Other Name: G-024

Experimental: Treatment B: Erdafitinib + Fluconazole
Participants will receive 400 mg fluconazole once daily orally from Day 1 to Day 11 in a fasted state and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 400 mg fluconazole dose.
Drug: Erdafitinib
A single 4-mg of erdafitinib tablet will be administered on Day 1 in Treatment A and on Day 5 in Treatment B and C.
Other Name: G-024

Drug: Fluconazole
A 400-mg fluconazole orally (4*100 mg capsules) will be administered from Day 1 to Day 11.

Experimental: Treatment C: Erdafitinib + Itraconazole
Participants will receive 200 mg itraconazole once daily orally from Day 1 to Day 11 and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 200 mg itraconazole dose.
Drug: Erdafitinib
A single 4-mg of erdafitinib tablet will be administered on Day 1 in Treatment A and on Day 5 in Treatment B and C.
Other Name: G-024

Drug: Itraconazole
A 200-mg itraconazole orally (2*100 mg capsules) will be administered from Day 1 to Day 11.




Primary Outcome Measures :
  1. Maximum Observed Plasma Analyte Concentration (Cmax) of Erdafitinib [ Time Frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose ]
    The Cmax is the maximum observed plasma analyte concentration.

  2. Area Under the Plasma Analyte Concentration-time Curve From the Time of 0 to one Week Post-doses [(AUC)0-168h] of Erdafitinib [ Time Frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose ]
    Area under the plasma analyte concentration-time curve from time 0 to one week post-dose (168 hours).

  3. Area Under the Plasma Analyte Concentration-time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration [(AUC)0-last] of Erdafitinib [ Time Frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose ]
    [(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 (Clast).

  4. Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time [(AUC)0-infinity] of Erdafitinib [ Time Frame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose ]
    [(AUC)0-infinity] is defined as the area under the analyte concentration-time curve from time 0 to infinite time, calculated as the sum of AUClast and Clast/lambda (z), in which Clast is the last observed quantifiable concentration and lambda (z) is 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events (AEs) as a Measure of Safety [ Time Frame: From screening to end of study (approximately up to 61 days) ]
    An adverse event 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Be healthy on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
  • Be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, other specific tests, blood coagulation or hematology 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. Healthy participants should be characterized by the following genotype regarding CYP2C9: *1/*1 (wild type), *1/*2 or *1/*3
  • If a woman, must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening and on Day 1
  • 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 last study drug administration
  • If a man who is sexually active, must agree to use a condom; and if a man who is sexually active with a woman of childbearing potential and who has not had a vasectomy, must agree to use a condom in combination with an adequate contraception method as deemed appropriate by the investigator, example, partner using effective contraception (defined as hormonal contraception [pill, patch, injection], intrauterine device, surgical sterilization) during the study and not to donate sperm for 5 months after the last study drug administration

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, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
  • 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
  • Clinically significant abnormal values for hematology or clinical chemistry at screening as deemed appropriate by the investigator
  • Clinically significant abnormal physical examination, vital signs, or triplicate 12-lead ECG at screening as deemed appropriate by the investigator
  • Donated blood or blood products or had substantial loss of blood (more than 500 [milliliter]mL) within 3 months before the first study drug administration or intention to donate blood or blood products during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03135106


Locations
Belgium
Clinical Pharmacology Unit
Merksem, Belgium, 2170
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03135106     History of Changes
Other Study ID Numbers: CR108299
2017-000117-23 ( EudraCT Number )
42756493EDI1007 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Itraconazole
Hydroxyitraconazole
Fluconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors