Phase 1
Completed N=29
Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule
Neoplasms
Source: ClinicalTrials.gov NCT03329001 ↗
Enrolled (actual)
29
Serious AEs
14.2%
Results posted
Apr 2024
Primary outcomePrimary: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Niraparib-Stage 1 PK Phase — 14900; 16100 Hours*nanogram per milliliter
Summary
This is a three stage, open label, randomized-sequence, single-crossover Phase 1 study to evaluate the relative bioavailability (BA) and Bioequivalence (BE) of niraparib administered as a tablet formulation compared to the reference capsule formulation currently marketed in the United States. Stage 3 evaluates the effect of a high-fat meal on niraparib pharmacokinetics (PK) following a single dose of the tablet. The Extension Phase of this study is to enable participants enrolled in the study to continue to receive treatment with niraparib tablets if they are tolerating it and, in the Investigator's opinion, may receive benefit.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for Niraparib-Stage 1 PK Phase |
14900; 16100 | — |
| PRIMARY Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0 to Inf]) for Niraparib-Stage 1 PK Phase |
16200; 17200 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Niraparib-Stage 1 PK Phase |
451; 467 | — |
| PRIMARY Time to Reach Maximum Observed Plasma Concentration (Tmax) for Niraparib-Stage 1 PK Phase |
4.05; 4.00 | — |
| PRIMARY Terminal Half-life (T1/2) for Niraparib-Stage 1 PK Phase |
47.3; 43.8 | — |
| PRIMARY Apparent Total Body Clearance (CL/F) for Niraparib-Stage 1 PK Phase |
18.5; 17.4 | — |
| PRIMARY Apparent Terminal Volume of Distribution (Vz/F) for Niraparib-Stage 1 PK Phase |
1260; 1100 | — |
| PRIMARY AUC(0-t) for Niraparib-Stage 2 PK Phase |
17070; 17730 | — |
| PRIMARY AUC(0 to Inf) for Niraparib-Stage 2 PK Phase |
17760; 18470 | — |
| PRIMARY Cmax for Niraparib-Stage 2 PK Phase |
519.5; 538.4 | — |
| PRIMARY Tmax for Niraparib-Stage 2 PK Phase |
5.00; 4.97 | — |
| PRIMARY T1/2 for Niraparib-Stage 2 PK Phase |
47.94; 50.17 | — |
| PRIMARY CL/F for Niraparib-Stage 2 PK Phase |
16.89; 16.25 | — |
| PRIMARY Vz/F for Niraparib-Stage 2 PK Phase |
1128; 1128 | — |
| PRIMARY AUC(0-t) for Niraparib-Stage 3 PK Phase |
20100; 25990 | — |
| PRIMARY AUC(0 to Inf) for Niraparib-Stage 3 PK Phase |
23600; 29770 | — |
| PRIMARY Cmax for Niraparib-Stage 3 PK Phase |
704.1; 774.6 | — |
| PRIMARY Tmax for Niraparib-Stage 3 PK Phase |
4.88; 5.97 | — |
| PRIMARY T1/2 for Niraparib-Stage 3 PK Phase |
46.39; 46.08 | — |
| PRIMARY CL/F for Niraparib-Stage 3 PK Phase |
12.71; 10.08 | — |
| PRIMARY Vz/F for Niraparib-Stage 3 PK Phase |
833.8; 651.4 | — |
| PRIMARY Time From Administration of the Dose to the First Quantifiable Concentration (Tlag) for Niraparib-Stage 3 PK Phase |
0.00; 0.00 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs-Stage 1 PK Phase (Periods 1 and 2 Only) |
9; 12; 0; 0 | — |
| SECONDARY Number of Participants With TEAEs Leading to Discontinuation -Stage 1 PK Phase (Periods 1 and 2 Only) |
0; 0 | — |
| SECONDARY Number of Participants With TEAEs and Serious TEAEs-Stage 2 PK Phase (Periods 1 and 2 Only) |
86; 73; 10; 10 | — |
| SECONDARY Number of Participants With TEAEs-leading to Discontinuation Stage 2 PK Phase (Periods 1 and 2 Only) |
2; 2 | — |
| SECONDARY Number of Participants With TEAEs and Serious TEAEs-Stage 3 PK Phase (Periods 1 and 2 Only) |
8; 12; 4; 2 | — |
| SECONDARY Number of Participants With TEAEs-leading to Discontinuation Stage 3 PK Phase (Periods 1 and 2 Only) |
1; 1 | — |
| SECONDARY Number of Participants With TEAEs and Serious TEAEs - Extension Phase |
120; 65; 40; 20 | — |
| SECONDARY Number of Participants With TEAEs-leading to Discontinuation - Extension Phase |
8; 9 | — |
Eligibility Criteria
Key inclusion criteria
PK Phase: To be considered eligible to participate in this study, all of the following requirements must be met:
- Participants with histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors that have failed to respond to standard therapy, has progressed despite standard therapy, or for which no standard therapy exists, and who may benefit from treatment with a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor as assessed by the Investigator.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Adequate organ function as defined: Absolute neutrophil count ≥ 1,500 per microliter (/μL) (For Stage 3: >=1000/μL); Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 grams per deciliter (g/dL) (5.6 millimolar [mM]); Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 milliliters per minute (mL/min) using the Cockcroft-Gault equation or 24-hour urine creatinine clearance.; Total bilirubin ≤ 1.5 × ULN except in participants with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤ 5 × ULN.
- Participant has recovered to Grade 1 toxicity from prior cancer therapy (a participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
- Female participant of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug.
- Male participant agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug.
- (For Stage 3): CNS inclusion - Based on screening brain magnetic resonance imaging indicating no evidence of brain metastasis or needing immediate local therapy.
- Participant is able to eat a high fat meal.
- Participant is able to fast for a minimum of 10 hours before start of visit and for an additional 4 hours after study visit.
Extension Phase:
- ECOG performance status of 0 to 2.
- Adequate organ function as defined: Absolute neutrophil count ≥ 1,500/μL (For Stage 3: >=1000/μL); Platelets ≥ 100,000/μL; Hemoglobin ≥ 9 g/dL (5.6 mM); serum creatinine ≤ 1.5 × the ULN or a calculated creatinine clearance ≥ 60 mL/min (For Stage 3: ≥ 30 mL/min) using the Cockcroft-Gault equation or 24-hour urine creatinine clearance; Total bilirubin ≤ 1.5 × ULN except in participant with Gilbert's syndrome. Participants with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin; AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤5 × ULN
- Female participant of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug.
- Male participant agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug.
Key Exclusion Criteria: PK Phase:
- Known diagnosis of immunodeficiency
- Symptomatic uncontrolled brain or leptomeningeal metastases.
- Major surgery within 3 weeks of starting the study or participant has not recovered from any effects of any major surgery.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection.
- Known history of myelodysplastic syndrome or acute myeloid leukemia.
- Part
Data sourced from ClinicalTrials.gov (NCT03329001). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.