Prostatic Neoplasms
Conditions
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.
Interventions
DRUGNiraparib
Niraparib will be administered orally.
Abiraterone Acetate will be administered orally.
DRUGPrednisone
Prednisone will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 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. |
| 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. |
| 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. |
Countries
Belgium, France, Georgia, Moldova, Netherlands, Poland, Spain, Sweden, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed