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

Primary Purpose

Hepatic Impairment

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Erdafitinib

About this trial

This is an interventional other trial for Hepatic Impairment

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

CRS Clinical Research Services Kiel GmbH
APEX GmbH

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Cohort 1: Normal Hepatic Function

Cohort 2: Mild Hepatic Impairment

Cohort 3: Moderate Hepatic Impairment

Cohort 4: Severe Hepatic Impairment

Arm Description

Participants with normal hepatic function will receive 6 milligram (mg) erdafitinib as a single oral dose under fasted conditions on Day 1.

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax)

Cmax is the maximum observed plasma concentration.

Time to Reach the Maximum Observed Plasma Concentration (Tmax)

Tmax is the time to reach maximum observed plasma concentration.

Area Under Plasma Concentration-Time Curve (AUC)

AUC is area under plasma concentration-time curve.

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).

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).

Apparent Volume of Distribution (Vd/F)

Vd/F is apparent volume of distribution after extravascular administration, uncorrected for absolute BA.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT03587363

First Posted

July 4, 2018

Last Updated

March 26, 2021

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03587363

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Terminated

Why Stopped

Mild/moderate hepatic impairment (HI) cohorts completed with no impact to erdafitinib exposure. Severe HI cohort enrollment stopped early.

Study Start Date

December 6, 2018 (Actual)

Primary Completion Date

December 22, 2020 (Actual)

Study Completion Date

December 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1: Normal Hepatic Function

Arm Type

Experimental

Arm Description

Participants with normal hepatic function will receive 6 milligram (mg) erdafitinib as a single oral dose under fasted conditions on Day 1.

Arm Title

Cohort 2: Mild Hepatic Impairment

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 3: Moderate Hepatic Impairment

Arm Type

Experimental

Arm Description

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.

Arm Title

Cohort 4: Severe Hepatic Impairment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Erdafitinib

Other Intervention Name(s)

JNJ-42756493

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax)

Description

Cmax is the maximum observed plasma concentration.

Time Frame

Up to 21 days

Title

Time to Reach the Maximum Observed Plasma Concentration (Tmax)

Description

Tmax is the time to reach maximum observed plasma concentration.

Time Frame

Up to 21 days

Title

Area Under Plasma Concentration-Time Curve (AUC)

Description

AUC is area under plasma concentration-time curve.

Time Frame

Up to 21 days

Title

Terminal Elimination Half-life (t1/2term, Lambda)

Description

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).

Time Frame

Up to 21 days

Title

Total Plasma Clearance (CL/F)

Description

CL/F is total plasma clearance of drug after extravascular administration, uncorrected for absolute bioavailability (BA), calculated as Dose/AUC (0-infinity).

Time Frame

Up to 21 days

Title

Apparent Volume of Distribution (Vd/F)

Description

Vd/F is apparent volume of distribution after extravascular administration, uncorrected for absolute BA.

Time Frame

Up to 21 days

Secondary Outcome Measure Information:

Title

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Description

Time Frame

Approximately 50 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

Facility Name

CRS Clinical Research Services Kiel GmbH

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

APEX GmbH

City

Munchen

ZIP/Postal Code

81241

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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