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

NCT04577833

Description:

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).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04577833

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CR108783
  • SECONDARY ID: 2019-000137-39
  • SECONDARY ID: 67652000PCR1001
  • NCT ID: NCT04577833

Conditions

  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
NiraparibTreatment Sequence ABD
Abiraterone Acetate (AA)Treatment Sequence ABD
PrednisoneTreatment Sequence ABD

Purpose

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 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.

Trial Arms

NameTypeDescriptionInterventions
Treatment Sequence ABDExperimentalParticipants 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.
  • Niraparib
  • Abiraterone Acetate (AA)
  • Prednisone
Treatment Sequence ADBExperimentalParticipants 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.
  • Niraparib
  • Abiraterone Acetate (AA)
  • Prednisone
Treatment Sequence CBDExperimentalParticipants 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.
  • Niraparib
  • Abiraterone Acetate (AA)
  • Prednisone
Treatment Sequence CDBExperimentalParticipants 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.
  • Niraparib
  • Abiraterone Acetate (AA)
  • Prednisone

Eligibility 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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Cmax,ss is defined as maximum observed analyte concentration at steady state.

Secondary Outcome Measures

Measure:Maximum Observed Analyte Concentration at (Cmax) of Niraparib and AA (Period 1)
Time Frame:Predose, up to 72 hours post dose
Safety Issue:
Description:Cmax is defined as maximum observed analyte concentration.
Measure: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
Safety Issue:
Description:AUC (0-72h) is defined as area under the plasma concentration-time curve from time zero to 72 hours post dosing.
Measure:Ratio of individual AUC (0-72h) Values Between Test and Reference Treatment (Period 1)
Time Frame:Predose, up to 72 hours post dose
Safety Issue:
Description:Ratio of individual AUC (0-72h) values between test and reference treatment will be assessed.
Measure:Serum Testosterone Level
Time Frame:Predose on Day -7, Day 11, Day 12 and Day 23
Safety Issue:
Description:Serum testosterone level will be assessed.
Measure: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)
Safety Issue:
Description: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.
Measure:Number of Participants with AEs by Severity
Time Frame:From study start until study completion (up to 1.4 years)
Safety Issue:
Description: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.
Measure:Number of Participants with Clinical Laboratory Abnormalities
Time Frame:From study start until study completion (up to 1.4 years)
Safety Issue:
Description:Number of participants with clinical laboratory abnormalities including hematology, serum chemistry and urinalysis will be reported.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

August 11, 2021