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

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: Niraparib IV (Labeled); Drug: Niraparib Oral Capsules (Labeled); Drug: Niraparib Oral Capsules (Unlabeled)

• Registration Number: NCT02476552
• Lead Sponsor: Tesaro, Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-05-29
• Study First Submitted QC: 2015-06-18
• Study First Posted: 2015-06-19
• Primary Completion: 2015-12
• Study Completion: 2018-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-08
• Last Update Posted: 2020-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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.

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Niraparib Oral and IV	Niraparib IV (Labeled)	Single Oral dose of Niraparib capsules (unlabeled active pharmaceutical ingredient) orally and a 15-minute IV infusion of Niraparib (labeled active pharmaceutical ingredient)
Niraparib Oral and IV	Niraparib Oral Capsules (Unlabeled)	Single Oral dose of Niraparib capsules (unlabeled active pharmaceutical ingredient) orally and a 15-minute IV infusion of Niraparib (labeled active pharmaceutical ingredient)
Niraparib Oral	Niraparib Oral Capsules (Labeled)	Single Oral dose of Niraparib capsules (labeled active pharmaceutical ingredient)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
AUC0-last	0 - 22 days	AUC (Area Under the Curve) from time 0 to the last quantifiable concentration
Cmax	0 - 22 days	Observed Maximum plasma Concentration

Trial Locations

Locations (1)

The Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands