Castration-Resistant Prostate CancerPhase 1NCT02578797
A JNJ-56021927 (ARN-509; Apalutamide) QT/QTc Study
A Phase 1 study testing Apalutamide in people with Castration-Resistant Prostate Cancer, run by Aragon Pharmaceuticals, Inc. at 5 sites in 5 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-Resistant Prostate Cancer
- What is being tested?
- Apalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 18 Dec 2015to 13 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
Official title: 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)
Read the 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.
- Conditions
- Castration-Resistant Prostate Cancer
- Being tested
- Apalutamide
- Keywords
- Castration-Resistant Prostate Cancer (CRPC), Prostatic Neoplasms, Genital Diseases, Male, Genital Neoplasms, Male, Neoplasms, Neoplasms by Site, Prostatic Diseases, Urogenital Neoplasms
- Medical subject headings
- Prostatic Neoplasms, Genital Diseases, Male, Genital Neoplasms, Male, Neoplasms, Neoplasms by Site, Prostatic Diseases, Urogenital Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApalutamideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Apalutamide | Experimental | 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. Receives: Drug: Apalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)
Secondary outcomes (9)
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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Cmin will only be collected on Day 1, Cycle 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study start18 Dec 2015
- Primary completion20 Sep 2016
- Study completion13 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration-Resistant Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aragon Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02578797
- Sponsor's protocol ID
- CR108049
- Other IDs
- 2015-004044-19, 56021927PCR1019, 2015
- Status last verified
- Nov 2023
- First submitted
- 15 Oct 2015
- Last updated
- 9 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 1b QT/QTc Study of JNJ-56021927 (ARN-509) in Subjects With Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT02578797
- Acronym / sponsor ID
- CR108049
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Aragon Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Dec 2015 (actual)
- Primary completion
- 20 Sep 2016 (actual)
- Study completion
- 13 Oct 2022 (actual)
- First posted
- 19 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Apalutamide | Experimental | Drug: ApalutamideProstate 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApalutamideStudy drug will be administered orally at a dose level of 240 mg daily (4 x 60 mg tablets) in treatment cycles of 28 days. | Drug | Apalutamide |
Primary outcome
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.
9 secondary outcomes
Electrocardiographic parameters (HR, RR, PR, and QRS)
Time frame: 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)
Electrocardiographic parameters T- and U-wave morphology
Time frame: 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)
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).
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)
Pharmacokinetic parameter maximum concentration observed (Cmax)
Time frame: 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)
Pharmacokinetic parameter minimum observed plasma concentration (Cmin)
Time frame: Cmin will only be collected on Day 1, Cycle 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Apalutamide in people with Castration-Resistant Prostate Cancer, run by Aragon Pharmaceuticals, Inc. at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada, Moldova, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
QTc Fridericia (QTcF) parameter (time frame: Day-1 and Day 1 (Cycle 1) and Day 1 (Cycle 3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2023.