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).
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Niraparib | | Treatment Sequence ABD |
| Abiraterone Acetate (AA) | | Treatment Sequence ABD |
| Prednisone | | Treatment Sequence ABD |
Purpose
The purpose of this study is to determine the bioequivalence (BE) and relative
bioavailability (rBA) 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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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 Phase, all participants will continue to receive treatment with niraparib and AA plus prednisone. | - Niraparib
- Abiraterone Acetate (AA)
- 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 Phase all participants will continue to receive treatment with niraparib plus AA along with prednisone. | - Niraparib
- Abiraterone Acetate (AA)
- 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 Phase all participants will continue to receive treatment with niraparib plus AA along with prednisone. | - Niraparib
- Abiraterone Acetate (AA)
- 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 Phase all participants will continue to receive treatment with niraparib plus AA along with prednisone. | - 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
- Toxicity associated with prior chemotherapy or radiotherapy has resolved to Grade <= 1
(except alopecia, local skin fibrosis/reaction or Grade <= 2 neuropathy) at screening
Exclusion Criteria:
- Symptomatic brain metastases
- Prior disease progression during treatment with abiraterone acetate (AA) and 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 abiraterone acetate
(AA) or the corresponding excipients of niraparib/AA
- Evidence of serious active viral, bacterial or uncontrolled systemic fungal infection
- Active hepatitis B virus (example, hepatitis B surface antigen [HBsAg] reactive) or
active hepatitis C virus (HCV) (example, HCV ribonucleic acid [RNA] [qualitative] is
detected)
| 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 168 Hours (AUC [0-168h]) of Niraparib and AA (Period 1) |
| Time Frame: | Predose, up to 168 hours post dose |
| Safety Issue: | |
| Description: | AUC (0-168h) is defined as area under the plasma concentration-time curve from time zero to 168 hours post dosing. |
| Measure: | Ratio of individual AUC (0-168h) Values Between Test and Reference Treatment (Period 1) |
| Time Frame: | Predose, up to 168 hours post dose |
| Safety Issue: | |
| Description: | Ratio of individual AUC (0-168h) values between test and reference treatment will be assessed. |
| Measure: | Serum Testosterone Level |
| Time Frame: | Predose on Day -7, Day 15 and Day 29 |
| 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 3.8 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 3.8 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 3.8 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: | Not yet recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
October 5, 2020
