Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03329001
• Collaborator: (none)
• Enrollment: 236
• Locations: 16
• Arms: 6
• Anticipated Duration (Months): 65.2
• Patients Per Site: 14.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Niraparib Tablet; Drug: Niraparib Capsule	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 236 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized-Sequence, Multicenter, Single-Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Formulation Compared to Niraparib Capsule Formulation in Patients With Advanced Solid Tumors
• Actual Study Start Date: Nov 29, 2017
• Actual Primary Completion Date: Dec 30, 2021
• Anticipated Study Completion Date: May 8, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stage 1: Tablet-Capsule Sequence Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase	Drug: Niraparib Tablet; Niraparib tablet formulation; Drug: Niraparib Capsule; Niraparib capsule formulation
Experimental: Stage 1: Capsule-Tablet Sequence Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase	Drug: Niraparib Tablet; Niraparib tablet formulation; Drug: Niraparib Capsule; Niraparib capsule formulation
Experimental: Stage 2: Tablet-Capsule Sequence Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase.	Drug: Niraparib Tablet; Niraparib tablet formulation; Drug: Niraparib Capsule; Niraparib capsule formulation
Experimental: Stage 2: Capsule-Tablet Sequence Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase	Drug: Niraparib Tablet; Niraparib tablet formulation; Drug: Niraparib Capsule; Niraparib capsule formulation
Experimental: Stage 3: High fat meal-fasted sequence Single dose niraparib tablet with a high fat meal followed by single dose of niraparib tablet in a fasted state.	Drug: Niraparib Tablet; Niraparib tablet formulation
Experimental: Stage 3: Fasted-high fat meal sequence Single dose niraparib tablet in a fasted state followed by single dose Niraparib tablet with a high fat meal.	Drug: Niraparib Tablet; Niraparib tablet formulation

Outcome Measures

Primary Outcome Measures

1. Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC[0-t]) for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

2. Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0 to inf]) for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

3. Maximum observed plasma concentration (Cmax) for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

4. Time to reach maximum observed plasma concentration (Tmax) for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

5. Terminal elimination half-life (T1/2) for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

6. Apparent total body clearance for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

7. Apparent terminal volume of distribution for niraparib-Stages 1, 2 and 3 PK Phase [Up to 168 hours post-dose]

8. Time from administration of the dose to the first quantifiable concentration (Tlag) for niraparib-Stage 3 PK Phase [Up to 168 hours post-dose]

Secondary Outcome Measures

1. Number of participants with treatment emergent adverse events (TEAEs), serious TEAEs and discontinuations due to TEAEs-Stages 1, 2 and 3 PK Phase [Up to 54 days]

2. Number of participants with TEAEs, serious TEAEs and discontinuations due to TEAEs-Extension Phase [Approximately 1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

• Participant is currently taking any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor, and verapamil (Does not apply for Extension Phase).

• Participant taking proton pump inhibitors, antacids, or histamine 2 blockers within 48 hours prior to study drug administration (Does not apply for Extension Phase).

• Participant has gastric, gastro-esophageal or esophageal cancer; participant is unable to swallow orally administered medication; or participant has gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of niraparib.

• Participant has known active hepatic disease

• Participant has a past or current history of chronic alcohol use.

• Participant has significant pleural effusion or ascites that is expected to require drainage during the PK Phase (Does not apply for Extension Phase).

• For Stage 3 only: Participant is currently taking a lipase inhibitor or cholesterol absorption inhibitor, such as orlistat or ezetimibe, respectively. (Does not apply for participation in Extension Phase of this study).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Encinitas	California	United States	92024
2	GSK Investigational Site	Fresno	California	United States	93720
3	GSK Investigational Site	San Marcos	California	United States	92069
4	GSK Investigational Site	Denver	Colorado	United States	80218
5	GSK Investigational Site	New Haven	Connecticut	United States	06520
6	GSK Investigational Site	Sarasota	Florida	United States	34232
7	GSK Investigational Site	Atlanta	Georgia	United States	30322
8	GSK Investigational Site	Grand Rapids	Michigan	United States	49546
9	GSK Investigational Site	Jackson	Mississippi	United States	39216
10	GSK Investigational Site	Cincinnati	Ohio	United States	45267
11	GSK Investigational Site	Cleveland	Ohio	United States	44106
12	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73104
13	GSK Investigational Site	Nashville	Tennessee	United States	37203
14	GSK Investigational Site	Dallas	Texas	United States	75230
15	GSK Investigational Site	Houston	Texas	United States	77030
16	GSK Investigational Site	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Tesaro, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT03329001
• Other Study ID Numbers: 213362; 3000-01-004
• First Posted: Nov 1, 2017
• Last Update Posted: Jul 25, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tesaro, Inc.: PARP inhibitor; niraparib; Solid Tumor; Zejula
• Additional relevant MeSH terms: Niraparib

Study Results

No Results Posted as of Jul 25, 2022