A Study of Comparative Formulations of Niraparib and Abiraterone Acetate (AA) in Men With Prostate Cancer

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04577833
Collaborator
(none)
120
Enrollment
17
Locations
4
Arms
36.7
Anticipated Duration (Months)
7.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

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 phase (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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
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
Actual Study Start Date :
Nov 13, 2020
Anticipated Primary Completion Date :
Mar 2, 2022
Anticipated Study Completion Date :
Dec 6, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment Sequence ABD

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 Phase, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone.

Drug: Niraparib
Niraparib will be administered orally.

Drug: Abiraterone Acetate (AA)
Abiraterone Acetate will be administered orally.

Drug: Prednisone
Prednisone will be administered orally.

Experimental: Treatment Sequence ADB

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 Phase all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Drug: Niraparib
Niraparib will be administered orally.

Drug: Abiraterone Acetate (AA)
Abiraterone Acetate will be administered orally.

Drug: Prednisone
Prednisone will be administered orally.

Experimental: Treatment Sequence CBD

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 Phase all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Drug: Niraparib
Niraparib will be administered orally.

Drug: Abiraterone Acetate (AA)
Abiraterone Acetate will be administered orally.

Drug: Prednisone
Prednisone will be administered orally.

Experimental: Treatment Sequence CDB

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 Phase all participants will continue to receive treatment with niraparib and AAP or AAP alone.

Drug: Niraparib
Niraparib will be administered orally.

Drug: Abiraterone Acetate (AA)
Abiraterone Acetate will be administered orally.

Drug: Prednisone
Prednisone will be administered orally.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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

  1. 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.

  2. 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.

  3. 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.

  4. Serum Testosterone Level [Predose on Day -7, Day 11, Day 12 and Day 23]

    Serum testosterone level will be assessed.

  5. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [From study start until study completion (up to 1.4 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.

  6. Number of Participants with AEs by Severity [From study start until study completion (up to 1.4 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.

  7. Number of Participants with Clinical Laboratory Abnormalities [From study start until study completion (up to 1.4 years)]

    Number of participants with clinical laboratory abnormalities including hematology, serum chemistry and urinalysis will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts 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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1START Mountain RegionWest Valley CityUtahUnited States84119
2Universitair Ziekenhuis GentGentBelgium9000
3GZA Ziekenhuizen- Campus St AugustinusWilrijkBelgium2610
4Institut Bergonié, Centre de Lutte Contre le CancerBordeauxFrance33000
5HIA BeginSaint MandeFrance94163
6Arensia Exploratory MedicineTbilisiGeorgia0112
7Arensia Exploratory MedicineChisinauMoldova, Republic ofMd2025
8Erasmus MCRotterdamNetherlands3015 GD
9Uniwersyteckie Centrum KliniczneGdanskPoland80-214
10Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut BadawczyWarszawaPoland02-781
11Arensia Exploratory MedicineBucharestRomania21105
12Hosp. Univ. Fund. Jimenez DiazMadridSpain28040
13Hosp. Univ. Hm SanchinarroMadridSpain28050
14Hosp. Virgen de La VictoriaMálagaSpain29010
15Karolinska Universitetssjukhuset SolnaStockholmSweden171 76
16ARENSIA Exploratory Medicine UnitKievUkraine01135
17Sir Bobby Robson Unit, Northern Centre for Cancer CareNewcastle upon TyneUnited KingdomNE7 7DN

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT04577833
Other Study ID Numbers:
  • CR108783
  • 2019-000137-39
  • 67652000PCR1001
First Posted:
Oct 8, 2020
Last Update Posted:
Dec 3, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 3, 2021