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| ID | Type | Description | Link |
|---|---|---|---|
| 67652000PCR1001 | Other Identifier | Janssen Research & Development, LLC | |
| 2019-000137-39 | EudraCT Number | ||
| 2023-508150-26-00 | Registry Identifier | EUCT number |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Sequence ABD | Experimental | 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 | Experimental | 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 | Experimental | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Niraparib | Drug | Niraparib will be administered orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Analyte Concentration at Steady State (Cmax,ss) of Niraparib and Abiraterone Acetate (AA) [Period 2 and Period 3] | Cmax,ss is defined as maximum observed analyte concentration at steady state. | Predose, up to 10 hour post dose |
| 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) | AUC (0-24h),ss is defined as area under the plasma concentration-time curve from time zero to 24 hours at steady state. | Predose, up to 24 hours post dose |
| Ratio of Individual Cmax,ss Values Between Test and Reference Treatment (Period 2 and Period 3) | Ratio of individual Cmax,ss values between test and reference treatment will be assessed. | Predose, up to 10 hours post dose |
| Ratio of individual AUC (0-24h),ss Values Between Test and Reference Treatment (Period 2 and Period 3) | Ratio of individual AUC (0-24h),ss values between test and reference treatment will be assessed. | Predose, up to 24 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Analyte Concentration at (Cmax) of Niraparib and AA (Period 1) | Cmax is defined as maximum observed analyte concentration. | Predose, up to 72 hours post dose |
| Area Under the Plasma Concentration-time Curve from Time Zero to 72 Hours (AUC [0-72h]) of Niraparib and AA (Period 1) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| START Mountain Region | West Valley City | Utah | 84119 | United States | ||
| Universitair Ziekenhuis Gent |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38436924 | Derived | Yu A, Hazra A, Jiao JJ, Hellemans P, Mitselos A, Tian H, Ruixo JJP, Haddish-Berhane N, Ouellet D, Russu A. Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation. Clin Pharmacokinet. 2024 Apr;63(4):511-527. doi: 10.1007/s40262-023-01340-5. Epub 2024 Mar 4. |
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The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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| Experimental |
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. |
|
| Abiraterone Acetate (AA) | Drug | Abiraterone Acetate will be administered orally. |
|
| Prednisone | Drug | Prednisone will be administered orally. |
|
AUC (0-72h) is defined as area under the plasma concentration-time curve from time zero to 72 hours post dosing. |
| Predose, up to 72 hours post dose |
| Ratio of individual AUC (0-72h) Values Between Test and Reference Treatment (Period 1) | Ratio of individual AUC (0-72h) values between test and reference treatment will be assessed. | Predose, up to 72 hours post dose |
| Serum Testosterone Level | Serum testosterone level will be assessed. | Predose on Day -7, Day 11, Day 12 and Day 23 |
| Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | 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. | From study start until study completion (up to 3.1 years) |
| Number of Participants with AEs by Severity | 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. | From study start until study completion (up to 3.1 years) |
| Number of Participants with Clinical Laboratory Abnormalities | Number of participants with clinical laboratory abnormalities including hematology, serum chemistry and urinalysis will be reported. | From study start until study completion (up to 3.1 years) |
| Ghent |
| 9000 |
| Belgium |
| GZA Ziekenhuizen- Campus St Augustinus | Wilrijk | 2610 | Belgium |
| Institut Bergonié, Centre de Lutte Contre le Cancer | Bordeaux | 33000 | France |
| HIA Begin | Saint-Mandé | 94163 | France |
| Arensia Exploratory Medicine 1 | Tbilisi | 0112 | Georgia |
| Arensia Exploratory Medicine | Chisinau | Md2025 | Moldova |
| Erasmus MC | Rotterdam | 3015 GD | Netherlands |
| Uniwersyteckie Centrum Kliniczne | Gdansk | 80 214 | Poland |
| Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy | Warsaw | 02-781 | Poland |
| Hosp Univ Fund Jimenez Diaz | Madrid | 28040 | Spain |
| Hosp Univ Hm Sanchinarro | Madrid | 28050 | Spain |
| Hosp Virgen de La Victoria | Málaga | 29010 | Spain |
| Karolinska Universitetssjukhuset Solna | Stockholm | 171 76 | Sweden |
| ARENSIA Exploratory Medicine Unit | Kyiv | 01135 | Ukraine |
| Sir Bobby Robson Unit, Northern Centre for Cancer Care | Newcastle upon Tyne | NE7 7DN | United Kingdom |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C545685 | niraparib |
| D000069501 | Abiraterone Acetate |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
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