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

Prostatic Neoplasms Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04577833
• Other study ID #: CR108783
• Secondary ID: 2019-000137-3967
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 13, 2020
• Est. completion date: December 5, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 136
• Est. completion date: December 5, 2025
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	GZA Ziekenhuizen- Campus St Augustinus	Wilrijk
France	Institut Bergonié, Centre de Lutte Contre le Cancer	Bordeaux
France	HIA Begin	Saint Mande
Georgia	Arensia Exploratory Medicine	Tbilisi
Moldova, Republic of	Arensia Exploratory Medicine	Chisinau
Netherlands	Erasmus MC	Rotterdam
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Virgen de La Victoria	Málaga
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Ukraine	ARENSIA Exploratory Medicine Unit	Kyiv
United Kingdom	Sir Bobby Robson Unit, Northern Centre for Cancer Care	Newcastle upon Tyne
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  France,  Georgia,  Moldova, Republic of,  Netherlands,  Poland,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Area Under the Plasma Concentration-time Curve from Time Zero to 72 Hours (AUC [0-72h]) of Niraparib and AA (Period 1)	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
Secondary	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
Secondary	Serum Testosterone Level	Serum testosterone level will be assessed.	Predose on Day -7, Day 11, Day 12 and Day 23
Secondary	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)
Secondary	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)
Secondary	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)