search
Back to results

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

Primary Purpose

Castration-Resistant Prostate Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Apalutamide
Sponsored by
Aragon Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castration-Resistant Prostate Cancer focused on measuring Castration-Resistant Prostate Cancer (CRPC), Prostatic Neoplasms, Genital Diseases, Male, Genital Neoplasms, Male, Neoplasms, Neoplasms by Site, Prostatic Diseases, Urogenital Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Apalutamide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
Electrocardiographic parameters T- and U-wave morphology
Number and percentage of participants with changes from baseline
Plasma concentrations apalutamide (and its active metabolite JNJ-56142060)
Blood samples will be taken following dose administration.
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.
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.
Pharmacokinetic parameter maximum concentration observed (Cmax)
The Cmax is the maximum observed plasma concentration.
Pharmacokinetic parameter time to reach Cmax (tmax)
The tmax is the time to reach the maximum observed plasma concentration.
Pharmacokinetic parameter minimum observed plasma concentration (Cmin)
The Cmin is the minimum observed plasma concentration.

Full Information

First Posted
October 15, 2015
Last Updated
November 22, 2022
Sponsor
Aragon Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT02578797
Brief Title
A JNJ-56021927 (ARN-509; Apalutamide) QT/QTc Study
Official Title
An Open-Label Phase 1b QT/QTc Study of JNJ-56021927 (ARN-509) in Subjects With Castration-Resistant Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
December 18, 2015 (Actual)
Primary Completion Date
September 20, 2016 (Actual)
Study Completion Date
October 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aragon Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-Resistant Prostate Cancer
Keywords
Castration-Resistant Prostate Cancer (CRPC), Prostatic Neoplasms, Genital Diseases, Male, Genital Neoplasms, Male, Neoplasms, Neoplasms by Site, Prostatic Diseases, Urogenital Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apalutamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Apalutamide
Intervention Description
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.
Primary Outcome Measure Information:
Title
QTc Fridericia (QTcF) parameter
Description
Mean change from baseline in QTcF as measured based on triplicate electrocardiograms extracted from continuous 12-lead Holter monitor recordings after study drug intake.
Time Frame
Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Secondary Outcome Measure Information:
Title
Electrocardiographic parameters (HR, RR, PR, and QRS)
Description
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
Time Frame
Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Title
Electrocardiographic parameters (QT)
Description
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.
Time Frame
Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Title
Electrocardiographic parameters T- and U-wave morphology
Description
Number and percentage of participants with changes from baseline
Time Frame
Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Title
Plasma concentrations apalutamide (and its active metabolite JNJ-56142060)
Description
Blood samples will be taken following dose administration.
Time Frame
Day-1, Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Title
Number of participants with Adverse Events
Description
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.
Time Frame
Day-1, Day 1 and Day 15 (Cycle 1); Day 1 and Day 15 (Cycle 2) and Day 1 (Cycle 3).
Title
Pharmacokinetic parameter area under the plasma drug concentration-time curve (AUC) from time 0 to 24 hours
Description
The AUC(0-24h) is the area under the plasma concentration-time curve from time 0 to time 24 hours after dosing.
Time Frame
Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Title
Pharmacokinetic parameter maximum concentration observed (Cmax)
Description
The Cmax is the maximum observed plasma concentration.
Time Frame
Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Title
Pharmacokinetic parameter time to reach Cmax (tmax)
Description
The tmax is the time to reach the maximum observed plasma concentration.
Time Frame
Day 1 and Day 2 (Cycle 1) and Day 1 (Cycle 3)
Title
Pharmacokinetic parameter minimum observed plasma concentration (Cmin)
Description
The Cmin is the minimum observed plasma concentration.
Time Frame
Cmin will only be collected on Day 1, Cycle 3

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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:
City
Greenville
State/Province
South Carolina
Country
United States
City
Montreal
State/Province
Quebec
Country
Canada
City
Chisinau
Country
Moldova, Republic of
City
Rotterdam
Country
Netherlands
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs