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

November 8, 2023 updated by: Aragon Pharmaceuticals, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
QTc Fridericia (QTcF) parameter
Time Frame: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Electrocardiographic parameters (HR, RR, PR, and QRS)
Time Frame: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
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)
Time Frame: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
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
Time Frame: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
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)
Time Frame: Day-1, Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
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
Time Frame: Day-1, Day 1 and Day 15 (Cycle 1); Day 1 and Day 15 (Cycle 2) and Day 1 (Cycle 3).
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
Time Frame: Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
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)
Time Frame: Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
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)
Time Frame: Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
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)
Time Frame: Cmin will only be collected on Day 1, Cycle 3
The Cmin is the minimum observed plasma concentration.
Cmin will only be collected on Day 1, Cycle 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aragon Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 18, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 20, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 13, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 19, 2015

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

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