Absorption, Metabolism, Excretion, and the Determination of Absolute Bioavailability of Niraparib in Subjects With Cancer

Study Overview
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Brief Summary
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This is an open-label study with 2 parts, plus an extension study following completion of Parts 1 or 2, that is being conducted in approximately 12 subjects (6 subjects in Part 1; 6 subjects in Part 2) with cancer to examine the absorption, metabolism, excretion, and absolute bioavailability of niraparib.

Detailed Description
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Part 1: After an overnight fast of at least 10 hours, subjects will receive a single, oral dose of niraparib (unlabeled active pharmaceutical ingredient) on Day 1. Two hours after the oral dose, subjects will receive a 15-minute IV infusion of niraparib (labeled pharmaceutical ingredient). Part 2: After an overnight fast of at least 10 hours, subjects will receive a single, oral dose of niraparib, labeled active pharmaceutical ingredient.

Official Title
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Absorption, Metabolism, Excretion, and the Determination of Absolute Bioavailability of Niraparib in Subjects With Cancer

Conditions
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Cancer

Intervention / Treatment
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* Drug: Niraparib Oral Capsules (Labeled)
* Drug: Niraparib IV (Labeled)
* Drug: Niraparib Oral Capsules (Unlabeled)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject, male or female, is at least 18 years of age. Subject has histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors that have failed to respond to standard therapy, have progressed despite standard therapy, refuse standard therapy, or for which no standard therapy exists, and that may benefit from treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor. The diagnosis must be confirmed with a previous computed tomography (CT) scan. The subject has adequate organ function: Subject must have an ECOG performance status of 0 to 2. Female subjects of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [hCG]) within 72 hours prior to receiving the first dose of study drug. Exclusion Criteria: Subject has undergone palliative radiotherapy within 1 week of study drug administration, encompassing >20% of the bone marrow. Subject has persistent >Grade 2 toxicity from prior cancer therapy. Subject has known hypersensitivity to the components of niraparib. Subject has had major surgery within 3 weeks of study drug administration or has not recovered from all effects of any major surgery. Subject is considered a medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days of the Screening Visit) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Subject has participated in a radioactive clinical study and has received an investigational radiolabeled drug within 6 months prior to study drug administration (for subjects participating in Part 2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib Oral and IV<br>Single Oral dose of Niraparib capsules (unlabeled active pharmaceutical ingredient) orally and a 15-minute IV infusion of Niraparib (labeled active pharmaceutical ingredient) | Drug: Niraparib IV (Labeled)<br>* Intravenous (IV) infusion of 100 μg niraparib (containing approximately 1 μCi of [14C]-niraparib)<br>Drug: Niraparib Oral Capsules (Unlabeled)<br>* Single 300 mg dose of niraparib (unlabeled active pharmaceutical ingredient)<br>|
| Experimental: Niraparib Oral<br>Single Oral dose of Niraparib capsules (labeled active pharmaceutical ingredient) | Drug: Niraparib Oral Capsules (Labeled)<br>* Single 300 mg dose of niraparib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral bioavailability (F) will be derived using F=AUCoral / AUCiv as a % | Absolute bioavailability of niraparib will be calculated as the ratio of dose normalized oral to IV niraparib exposure | 0 - 22 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-last | AUC (Area Under the Curve) from time 0 to the last quantifiable concentration | 0 - 22 days | 
| Cmax | Observed Maximum plasma Concentration | 0 - 22 days |