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

NCT04577833 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10878367652000PCR10012019-000137-392023-508150-26-00
• Study Type: interventional
• Target: 136
• Locations: 11 countries
• Sites: 16

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).

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (7)

• Maximum Observed Analyte Concentration at (Cmax) of Niraparib and AA (Period 1)

  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)

  Predose, up to 72 hours post dose

• Ratio of individual AUC (0-72h) Values Between Test and Reference Treatment (Period 1)

  Predose, up to 72 hours post dose

• Serum Testosterone Level

  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

  From study start until study completion (up to 3.1 years)

Study Arms (4)

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.

Drug: Niraparib; Drug: Abiraterone Acetate (AA); Drug: Prednisone

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.

Drug: Niraparib; Drug: Abiraterone Acetate (AA); Drug: Prednisone

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.

Drug: Niraparib; Drug: Abiraterone Acetate (AA); Drug: Prednisone

Treatment Sequence CDB

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.

Drug: Niraparib; Drug: Abiraterone Acetate (AA); Drug: Prednisone

Interventions

Prednisone DRUG

Prednisone will be administered orally.

Treatment Sequence ABD; Treatment Sequence ADB; Treatment Sequence CBD; Treatment Sequence CDB

Niraparib DRUG

Niraparib will be administered orally.

Treatment Sequence ABD; Treatment Sequence ADB; Treatment Sequence CBD; Treatment Sequence CDB

Abiraterone Acetate (AA) DRUG

Abiraterone Acetate will be administered orally.

Treatment Sequence ABD; Treatment Sequence ADB; Treatment Sequence CBD; Treatment Sequence CDB

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (16)

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

GZA Ziekenhuizen- Campus St Augustinus

Wilrijk, 2610, Belgium

Location

Institut Bergonié, Centre de Lutte Contre le Cancer

Bordeaux, 33000, France

Location

HIA Begin

Saint-Mandé, 94163, France

Location

Arensia Exploratory Medicine 1

Tbilisi, 0112, Georgia

Location

Arensia Exploratory Medicine

Chisinau, Md2025, Moldova

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 214, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Hosp Univ Hm Sanchinarro

Madrid, 28050, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden

Location

ARENSIA Exploratory Medicine Unit

Kyiv, 01135, Ukraine

Location

Sir Bobby Robson Unit, Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38436924 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

niraparib; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 8, 2020
• Study Start: November 13, 2020
• Primary Completion: October 15, 2021
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); GE (1); GB (1); US (1); MO (1); PL (2); ES (3); FR (2); SE (1); UA (1); NL (1)