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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04577833
Recruitment Status : Active, not recruiting
First Posted : October 8, 2020
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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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 disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Niraparib Drug: Abiraterone Acetate (AA) Drug: Prednisone 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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 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 : November 13, 2020
Actual Primary Completion Date : October 15, 2021
Estimated Study Completion Date : December 6, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/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
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Primary Outcome Measures :
  1. Maximum Observed Analyte Concentration at Steady State (Cmax,ss) of Niraparib and Abiraterone Acetate (AA) [Period 2 and Period 3] [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04577833


Locations
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United States, Utah
START Mountain Region
West Valley City, Utah, United States, 84119
Belgium
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
GZA Ziekenhuizen- Campus St Augustinus
Wilrijk, Belgium, 2610
France
Institut Bergonié, Centre de Lutte Contre le Cancer
Bordeaux, France, 33000
HIA Begin
Saint Mande, France, 94163
Georgia
Arensia Exploratory Medicine
Tbilisi, Georgia, 0112
Moldova, Republic of
Arensia Exploratory Medicine
Chisinau, Moldova, Republic of, Md2025
Netherlands
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-214
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Warszawa, Poland, 02-781
Spain
Hosp. Univ. Fund. Jimenez Diaz
Madrid, Spain, 28040
Hosp. Univ. Hm Sanchinarro
Madrid, Spain, 28050
Hosp. Virgen de La Victoria
Málaga, Spain, 29010
Sweden
Karolinska Universitetssjukhuset Solna
Stockholm, Sweden, 171 76
Ukraine
ARENSIA Exploratory Medicine Unit
Kiev, Ukraine, 01135
United Kingdom
Sir Bobby Robson Unit, Northern Centre for Cancer Care
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04577833    
Other Study ID Numbers: CR108783
2019-000137-39 ( EudraCT Number )
67652000PCR1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 8, 2020    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Abiraterone Acetate
Niraparib
Anti-Inflammatory Agents
Glucocorticoids
 Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors