A JNJ-56021927 (ARN-509; Apalutamide) QT/QTc Study

An Open-Label Phase 1b QT/QTc Study of JNJ-56021927 (ARN-509) in Subjects With Castration-Resistant Prostate Cancer

The purpose of this study is to determine whether daily treatment with apalutamide affects the ventricular repolarization in participants with Castration-Resistant Prostate Cancer (CRPC)

Study Overview

• Status: Completed
• Conditions: Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: Apalutamide

Detailed Description

This is an open-label (a study in which the drug, procedure is known to participant and investigator), multicenter, Phase 1b study to investigate the effect of apalutamide on ventricular repolarization at a dose level of 240 milligram (mg daily). Approximately 42 participants with high-risk non-metastatic prostate cancer (NM-CRPC), defined as having a prostate specific antigen (PSA) doubling time less than or equal to (<=) 10 months, or participants with metastatic CRPC will be enrolled. The study consists of a 28-day Screening Phase, a Treatment Phase and a Follow-up Phase. In the Treatment Phase the study drug will be administrated in cycles of 28 days and the participants will be monitored for safety (including cardiac safety) and pharmacokinetics of the study drug. Adverse Events will be monitored throughout the study and in the Follow-up Phase until 30 days after the last dose of study drug. All participants will continue on study until disease progression, withdrawal of consent, lost to follow-up, the occurrence of unacceptable toxicity, the participant is no longer receiving clinical benefit in the opinion of the investigator, or termination of the study by the sponsor. Upon discontinuation of study drug, the participants will return for an End-of-Treatment (EoT) visit no later than 30 days after their last dose. The end of the study corresponds to the clinical cutoff and end of data collection.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
• Netherlands
  • Rotterdam, Netherlands
• United Kingdom
  • Sutton, United Kingdom
• United States
  • South Carolina
    • Greenville, South Carolina, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adenocarcinoma of the prostate; either non-metastatic castrate resistant prostate cancer (NM-CRPC) with high risk disease (defined as PSA Doubling time equal or less than (<=) 10 months) or metastatic CRPC
• Be surgically or medically castrated with testosterone levels of less than (<) 50 nanogram per deciliter
• If treated with a gonadotropin releasing hormone analog (ie, patient who has not undergone bilateral orchiectomy), then this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and must be continued throughout the study
• Electrocardiogram (ECG) showing a QT interval corrected for heart rate, using Fridericia formula (QTcF) <= 470 milliseconds (based on the average of a triplicate ECG set collected during the screening visit)
• Left ventricular ejection fraction (LVEF) of more than 45% as determined by multiple uptake gated acquisition (MUGA) or echocardiography at the screening visit

Exclusion Criteria:

• Abnormal cardiac function at screening
• Known brain metastases
• Has received an investigational drug within 4 weeks, or within a period < 10 times the drug's half-life, whichever is longer, of Cycle 1 Day 1
• Has received chemotherapy or immunotherapy for the treatment of prostate cancer within 4 weeks of Cycle 1 Day 1
• Prior treatment with enzalutamide and apalutamide
• Use of therapies that must be discontinued or substituted within at least 4 weeks prior to Cycle 1 Day 1 including medications to lower seizure threshold, inducing/inhibiting metabolizing enzymes or prolonging the QT interval
• History or condition that may predispose to seizures, or evidence of severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events within 12 months prior to Cycle 1 Day 1, New York Heart Association (NYHA) Class II to IV heart disease

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: Apalutamide; Prostate Cancer participants will receive the study drug on an outpatient basis except for Cycle 1 (Day 1 and Day 2) and Cycle 3 (Day 1), when intake must occur at study site under overnight fasted conditions.	Drug: Apalutamide; Study drug will be administered orally at a dose level of 240 mg daily (4 x 60 mg tablets) in treatment cycles of 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc Fridericia (QTcF) parameter	Mean change from baseline in QTcF as measured based on triplicate electrocardiograms extracted from continuous 12-lead Holter monitor recordings after study drug intake.	Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrocardiographic parameters (HR, RR, PR, and QRS)	A change from time-matched baseline measurements in HR, PR, RR and QRS interval will be determined on Day -1, Day 1 and Day 3	Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Electrocardiographic parameters (QT)	QT interval on a surface ECG will be corrected for heart rate using Bazett formula (QTcB) and study-specific Power (QTcP) if appropriate at each treatment period.	Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Electrocardiographic parameters T- and U-wave morphology	Number and percentage of participants with changes from baseline	Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Plasma concentrations apalutamide (and its active metabolite JNJ-56142060)	Blood samples will be taken following dose administration.	Day-1, Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Number of participants with Adverse Events	Participants will be monitored for safety during the Screening and Treatment Phases, and up to 30 days after the last dose of study drug. From Cycle 4 onward collection of Adverse Events (AEs) will be limited to Grade 3 or higher and all Serious AEs from the remainder of the study.	Day-1, Day 1 and Day 15 (Cycle 1); Day 1 and Day 15 (Cycle 2) and Day 1 (Cycle 3).
Pharmacokinetic parameter area under the plasma drug concentration-time curve (AUC) from time 0 to 24 hours	The AUC(0-24h) is the area under the plasma concentration-time curve from time 0 to time 24 hours after dosing.	Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Pharmacokinetic parameter maximum concentration observed (Cmax)	The Cmax is the maximum observed plasma concentration.	Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Pharmacokinetic parameter time to reach Cmax (tmax)	The tmax is the time to reach the maximum observed plasma concentration.	Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Pharmacokinetic parameter minimum observed plasma concentration (Cmin)	The Cmin is the minimum observed plasma concentration.	Cmin will only be collected on Day 1, Cycle 3

Collaborators and Investigators

• Sponsor: Aragon Pharmaceuticals, Inc.
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2015
• Primary Completion (Actual): September 20, 2016
• Study Completion (Actual): October 13, 2022

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 15, 2015
• First Posted (Estimated): October 19, 2015

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Neoplasms; Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Prostatic Diseases; Neoplasms by Site; Castration-Resistant Prostate Cancer (CRPC); Genital Diseases, Male
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CR108049; 2015-004044-19 (EudraCT Number); 56021927PCR1019 (Other Identifier: Aragon Pharmaceuticals, Inc)

Drug and device information, study documents

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