Clinical trial NCT04577833: A Study of Comparative Formulations of Niraparib and Abiraterone Acetate (AA) in Men With Prostate Cancer
Official title: An Open-label, Randomized Study to Assess the Relative Bioavailability (BA) and Bioequivalence (BE) of Comparative Formulations of Niraparib and Abiraterone Acetate (AA) in Men With Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 136
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to determine the relative bioavailability (rBA; Period 1) and bioequivalence (BE; Period 2 and 3) of various strengths and formulations of niraparib and abiraterone acetate (AA) at steady state under modified fasted conditions in participants with metastatic castration-resistant prostate cancer (mCRPC).

Detailed description: Niraparib is an orally available, highly selective poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. AA is a pro-drug of abiraterone which selectively inhibits the enzyme 17 alpha-hydroxylase/C17,20-lyase (CYP17), that is found in the testes and adrenals (leading to systemic inhibition of testosterone production), as well as in prostate tissues and tumors. The rationale of the study is to investigate the various strengths and formulations of niraparib and AA plus prednisone or prednisolone (P) in metastatic castration resistant prostate cancer (mCRPC) participants with and without homologous recombination repair (HRR) gene alterations. In participants with metastatic prostate cancer, DNA-repair anomalies are found in approximately 15 percent (%) to 20% of tumors. This study consists 4 periods: screening phase (up to 21 days); treatment phase (up to 22 days); extension and long-term extension phases (from day 23 until discontinuation); and post-treatment follow up phase (end of treatment \[EoT\] visit within 30 days after the last dose of study treatment). Total duration of study is up to 1.4 years. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specified time points during this study. Participants safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate
* Diagnosed with metastatic castration-resistant prostate cancer (mCRPC), who in the opinion of the investigator may benefit from treatment in this study
* Able to continue gonadotropin-releasing hormone analogues (GnRHa) therapy during the study if not surgically castrate (that is, participants who have not undergone bilateral orchiectomy)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (\<=) 1
* Willing to provide a tumor sample (archival) for determination of homologous recombination repair (HRR) gene alteration status

Exclusion Criteria:

* Symptomatic brain metastases
* Prior disease progression during treatment with abiraterone acetate (AA) alone or when combined with a poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi). Prior discontinuation of treatment with AA or PARPi due to AA- or PARPi related toxicity.
* History or current diagnosis of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML)
* Known allergies, hypersensitivity, or intolerance to niraparib or AA or the corresponding excipients of niraparib/AA
* Any medical condition that would make prednisone/prednisolone use contraindicated

Primary outcomes:
measure: Maximum Observed Analyte Concentration at Steady State (Cmax,ss) of Niraparib and Abiraterone Acetate (AA) [Period 2 and Period 3]
timeFrame: Predose, up to 10 hour post dose
measure: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours at Steady State (AUC [0-24h],ss) of Niraparib and AA (Period 2 and Period 3)
timeFrame: Predose, up to 24 hours post dose
measure: Ratio of Individual Cmax,ss Values Between Test and Reference Treatment (Period 2 and Period 3)
timeFrame: Predose, up to 10 hours post dose
measure: Ratio of individual AUC (0-24h),ss Values Between Test and Reference Treatment (Period 2 and Period 3)
timeFrame: Predose, up to 24 hours post dose
Secondary outcomes:
measure: Maximum Observed Analyte Concentration at (Cmax) of Niraparib and AA (Period 1)
timeFrame: Predose, up to 72 hours post dose
measure: Area Under the Plasma Concentration-time Curve from Time Zero to 72 Hours (AUC [0-72h]) of Niraparib and AA (Period 1)
timeFrame: Predose, up to 72 hours post dose
measure: Ratio of individual AUC (0-72h) Values Between Test and Reference Treatment (Period 1)
timeFrame: Predose, up to 72 hours post dose
measure: Serum Testosterone Level
timeFrame: Predose on Day -7, Day 11, Day 12 and Day 23
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: From study start until study completion (up to 3.1 years)
measure: Number of Participants with AEs by Severity
timeFrame: From study start until study completion (up to 3.1 years)
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: From study start until study completion (up to 3.1 years)
Other outcomes:
Locations:
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen- Campus St Augustinus
city: Bordeaux
country: France
facility: Institut Bergonié, Centre de Lutte Contre le Cancer
city: Saint Mande
country: France
facility: HIA Begin
city: Tbilisi
country: Georgia
facility: Arensia Exploratory Medicine
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp Univ Hm Sanchinarro
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Kyiv
country: Ukraine
facility: ARENSIA Exploratory Medicine Unit
city: Newcastle upon Tyne
country: United Kingdom
facility: Sir Bobby Robson Unit, Northern Centre for Cancer Care
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: