A Study of Comparative Formulations of Niraparib and Abiraterone Acetate (AA) in Men With Prostate Cancer
- Conditions
- Prostatic Neoplasms
- Interventions
- Registration Number
- NCT04577833
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 136
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence ABD Niraparib Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone. Treatment Sequence ABD Abiraterone Acetate (AA) Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone. Treatment Sequence ADB Abiraterone Acetate (AA) Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CBD Abiraterone Acetate (AA) Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CBD Prednisone Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CDB Niraparib Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CDB Abiraterone Acetate (AA) Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CDB Prednisone Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence ABD Prednisone Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone. Treatment Sequence ADB Niraparib Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence ADB Prednisone Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. Treatment Sequence CBD Niraparib Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone.
- Primary Outcome Measures
Name Time Method Maximum Observed Analyte Concentration at Steady State (Cmax,ss) of Niraparib and Abiraterone Acetate (AA) [Period 2 and Period 3] Predose, up to 10 hour post dose Cmax,ss is defined as maximum observed analyte concentration at steady state.
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) Predose, up to 24 hours post dose AUC (0-24h),ss is defined as area under the plasma concentration-time curve from time zero to 24 hours at steady state.
Ratio of Individual Cmax,ss Values Between Test and Reference Treatment (Period 2 and Period 3) Predose, up to 10 hours post dose Ratio of individual Cmax,ss values between test and reference treatment will be assessed.
Ratio of individual AUC (0-24h),ss Values Between Test and Reference Treatment (Period 2 and Period 3) Predose, up to 24 hours post dose Ratio of individual AUC (0-24h),ss values between test and reference treatment will be assessed.
- Secondary Outcome Measures
Name Time Method Ratio of individual AUC (0-72h) Values Between Test and Reference Treatment (Period 1) Predose, up to 72 hours post dose Ratio of individual AUC (0-72h) values between test and reference treatment will be assessed.
Serum Testosterone Level Predose on Day -7, Day 11, Day 12 and Day 23 Serum testosterone level will be assessed.
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability From study start until study completion (up to 3.1 years) An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with Clinical Laboratory Abnormalities From study start until study completion (up to 3.1 years) Number of participants with clinical laboratory abnormalities including hematology, serum chemistry and urinalysis will be reported.
Maximum Observed Analyte Concentration at (Cmax) of Niraparib and AA (Period 1) Predose, up to 72 hours post dose Cmax is defined as maximum observed analyte concentration.
Area Under the Plasma Concentration-time Curve from Time Zero to 72 Hours (AUC [0-72h]) of Niraparib and AA (Period 1) Predose, up to 72 hours post dose AUC (0-72h) is defined as area under the plasma concentration-time curve from time zero to 72 hours post dosing.
Number of Participants with AEs by Severity From study start until study completion (up to 3.1 years) Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death.
Trial Locations
- Locations (15)
Erasmus MC
🇳🇱Rotterdam, Netherlands
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
HIA Begin
🇫🇷Saint Mande, France
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Sweden
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
ARENSIA Exploratory Medicine Unit
🇺🇦Kyiv, Ukraine
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Hosp Univ Hm Sanchinarro
🇪🇸Madrid, Spain
Sir Bobby Robson Unit, Northern Centre for Cancer Care
🇬🇧Newcastle upon Tyne, United Kingdom
START Mountain Region
🇺🇸West Valley City, Utah, United States
Hosp Univ Fund Jimenez Diaz
🇪🇸Madrid, Spain
Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Institut Bergonié, Centre de Lutte Contre le Cancer
🇫🇷Bordeaux, France
GZA Ziekenhuizen- Campus St Augustinus
🇧🇪Wilrijk, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium