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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02476552
• Other study ID #: PR-30-5015-C
• Status: Completed
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: January 2018

Study information

• Verified date: January 2020
• Source: Tesaro, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2018
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Niraparib Oral Capsules (Labeled)
Single 300 mg dose of niraparib
• Niraparib IV (Labeled)
Intravenous (IV) infusion of 100 µg niraparib (containing approximately 1 µCi of [14C]-niraparib)
• Niraparib Oral Capsules (Unlabeled)
Single 300 mg dose of niraparib (unlabeled active pharmaceutical ingredient)

Locations

Country	Name	City	State
Netherlands	The Netherlands Cancer Institute	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Tesaro, Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AUC0-last	AUC (Area Under the Curve) from time 0 to the last quantifiable concentration	0 - 22 days
Secondary	Cmax	Observed Maximum plasma Concentration	0 - 22 days