Cancer
Conditions
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.
Interventions
DRUGNiraparib Oral Capsules (Labeled)
Single 300 mg dose of niraparib
DRUGNiraparib IV (Labeled)
Intravenous (IV) infusion of 100 μg niraparib (containing approximately 1 μCi of \[14C\]-niraparib)
DRUGNiraparib Oral Capsules (Unlabeled)
Single 300 mg dose of niraparib (unlabeled active pharmaceutical ingredient)
Sponsors
Tesaro, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Netherlands
Outcome results
None listed