Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase

Single dose niraparib capsule followed by single dose niraparib tablet followed by optional daily dosing extension phase

Single dose niraparib tablet followed by single dose niraparib capsule followed by optional daily dosing extension phase.

Single dose niraparib tablet with a high fat meal followed by single dose of niraparib tablet in a fasted state.

Single dose niraparib tablet in a fasted state followed by single dose Niraparib tablet with a high fat meal.

Niraparib Tablet

Niraparib Capsule

GSK Clinical Trials

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.

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

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

IPD for this study will be made available via the Clinical Study Data Request site.

Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0-t). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of AUC(0 to inf). Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of Cmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of Tmax. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of T1/2. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of CL/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of Vz/F. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

Blood samples were collected at indicated time points for pharmacokinetic assessment of tlag. Pharmacokinetic parameters were calculated using standard non-compartmental analysis.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablet and Niraparib capsule arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet and capsule, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs reported under Niraparib tablets under fasted and fed arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet fasted and fed, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Number of participants with TEAEs leading to discontinuation is reported. TEAEs reported under Niraparib tablets under fasted and fed arms include TEAEs with onset date during the corresponding period (Period 1 or Period 2) in which the participant received niraparib tablet fasted and fed, respectively.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that, at any dose; results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Data is not reported as participants response is still ongoing at the time of primary analysis.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Data is not reported as participants response is still ongoing at the time of primary analysis.

Tesaro, Inc.

Safety Population comprised of all participants who received any amount of niraparib during the PK Phase of the study. Results presented are based on primary analysis up to maximum 4.1 years. Results presented in this record correspond to the PK phase of the study. Analysis of end of study data is currently ongoing and will be provided in the study record after the analysis is completed.

Participants received a single oral dose of 300 mg niraparib tablet in a fasted state in either Period 1 or Period 2 of Stage 1 PK Phase.

Stage 1: Niraparib Tablet

Participants received a single oral dose of 300 mg (3x100 mg capsules) niraparib in a fasted state in either Period 1 or Period 2 of Stage 1 PK Phase.

Stage 1: Niraparib Capsule

Participants received a single oral dose of 300 mg niraparib tablet in a fasted state in either Period 1 or Period 2 of Stage 2 PK Phase.

Stage 2: Niraparib Tablet

Participants received a single oral dose of 300 mg (3x100 mg capsules) niraparib in a fasted state in either Period 1 or Period 2 of Stage 2 PK Phase.

Stage 2: Niraparib Capsule

Participants received a single oral dose of 300 mg niraparib tablet in a fasted state in either Period 1 or Period 2 of Stage 3 PK Phase.

Stage 3: Niraparib Tablet Fasted

Participants received a single oral dose of 300 mg niraparib tablet in a fed state with a high fat meal in either Period 1 or Period 2 of Stage 3 PK Phase.

Stage 3: Niraparib Tablet Fed

Participants received a single oral dose of 300 milligrams (mg) niraparib tablet in a fasted state in Period 1, followed by a wash-out period of 7 days. In Period 2, participants received a single oral dose of 3 capsules of 100 mg niraparib in a fasted state followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the extension phase were followed for up to 30 days (safety follow-up \[f/u\]) while participants eligible for extension phase proceeded for extension phase screening. Eligible participants then entered the extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 1: Niraparib Tablet/Capsule

Participants received a single oral dose of 3x100 mg niraparib capsules in a fasted state in Period 1, followed by a wash-out period of 7 days. In Period 2, participants received a single oral dose of 300 mg niraparib tablet in a fasted state followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the extension phase were followed for up to 30 days (safety f/u) while participants eligible for extension phase proceeded for extension phase screening. Eligible participants then entered the extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 1: Niraparib Capsule/Tablet

Participants received a single oral dose of 300 mg niraparib tablet in a fasted state in Period 1, followed by a wash-out period of 14 days. In Period 2, participants received a single oral dose of 3 capsules of 100 mg niraparib in a fasted state followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the Extension phase were followed for up to 30 days (safety f/u) while participants eligible for Extension phase proceeded for Extension phase screening. Eligible participants then entered the Extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 2: Niraparib Tablet/Capsule

Participants received a single oral dose of three 100 mg niraparib capsules in a fasted state in Period 1, followed by a wash-out period of 14 days. In Period 2, participants received a single oral dose of 300 mg niraparib tablet in a fasted state followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the Extension phase were followed for up to 30 days (safety f/u) while participants eligible for Extension phase proceeded for Extension phase screening. Eligible participants then entered the Extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 2: Niraparib Capsule/Tablet

Participants received a single oral dose of 300 mg niraparib tablet in a fasted state in Period 1, followed by a wash-out period of 14 days. In period 2, participants received a single oral dose of 300 mg niraparib tablet in a fed state with a high fat meal followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the Extension phase were followed for up to 30 days (safety f/u) while participants eligible for Extension phase proceeded for Extension phase screening. Eligible participants then entered the Extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 3: Niraparib Tablet Fasted/Fed

Participants received a single oral dose of 300 mg niraparib tablet in a fed state with a high fat meal in Period 1, followed by a wash-out period of 14 days. In period 2, participants received a single oral dose of 300 mg niraparib tablet in a fasted state followed by a 7-day wash-out period. After the last dose of niraparib, participants who did not enter the Extension phase were followed for up to 30 days (safety f/u) while participants eligible for Extension phase proceeded for Extension phase screening. Eligible participants then entered the Extension Phase, where they received 300 mg or 200 mg niraparib tablets or capsules for once daily dosing depending on their body weight and platelet count.

Stage 3: Niraparib Tablet Fed/Fasted

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Baseline characteristics were presented for Safety Population, all participants who received any amount of niraparib during the PK phase of study.

GSK Response Center

Bioavailability (BA) Evaluable Population included all participants who completed both PK Periods and had sufficient PK sample collection to accurately estimate PK parameters, without significant niraparib carryover (Baseline concentration \>5 percent (%) of maximum observed plasma concentration \[Cmax\]), in both Periods.

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

Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0 to Inf]) for Niraparib-Stage 1 PK Phase

Maximum Observed Plasma Concentration (Cmax) for Niraparib-Stage 1 PK Phase

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Niraparib-Stage 1 PK Phase

Terminal Half-life (T1/2) for Niraparib-Stage 1 PK Phase

Apparent Total Body Clearance (CL/F) for Niraparib-Stage 1 PK Phase

Apparent Terminal Volume of Distribution (Vz/F) for Niraparib-Stage 1 PK Phase

Bioequivalence (BE) Evaluable Population included all participants who completed both the Study Drug and Washout/PK and had sufficient PK sample collection to accurately estimate PK parameters, without significant niraparib carryover and without events or protocol deviations deemed affect PK, in both Periods. Only those participants with estimable PK parameter data in both periods were analyzed.

AUC(0-t) for Niraparib-Stage 2 PK Phase

BE Evaluable Population. Only those participants with estimable PK parameter data available in both Periods were analyzed.

AUC(0 to Inf) for Niraparib-Stage 2 PK Phase

Cmax for Niraparib-Stage 2 PK Phase

Tmax for Niraparib-Stage 2 PK Phase

T1/2 for Niraparib-Stage 2 PK Phase

CL/F for Niraparib-Stage 2 PK Phase

Vz/F for Niraparib-Stage 2 PK Phase

Food Effect (FE) Evaluable Population included all participants who completed both PK periods and had sufficient PK sample collection to accurately estimate PK parameters in both periods. Participants meeting non-evaluability criteria or having significant niraparib carryover (Baseline concentration \>5% of Cmax) were completely excluded from the FE Population. Only those participants with estimable PK parameter data available in both Periods were analyzed.

AUC(0-t) for Niraparib-Stage 3 PK Phase

FE Evaluable Population. Only those participants with estimable PK parameter data available in both Periods were analyzed.

AUC(0 to Inf) for Niraparib-Stage 3 PK Phase

Cmax for Niraparib-Stage 3 PK Phase

Tmax for Niraparib-Stage 3 PK Phase

T1/2 for Niraparib-Stage 3 PK Phase

CL/F for Niraparib-Stage 3 PK Phase

Vz/F for Niraparib-Stage 3 PK Phase

Time From Administration of the Dose to the First Quantifiable Concentration (Tlag) for Niraparib-Stage 3 PK Phase

TEAE

Serious TEAE

Safety Population comprised of all participants who received any amount of niraparib during the Stage 1 PK Phase of the study.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs-Stage 1 PK Phase (Periods 1 and 2 Only)

Number of Participants With TEAEs Leading to Discontinuation -Stage 1 PK Phase (Periods 1 and 2 Only)

Safety Population comprised of all participants who received any amount of niraparib during the Stage 2 PK Phase of the study.

Number of Participants With TEAEs and Serious TEAEs-Stage 2 PK Phase (Periods 1 and 2 Only)

Number of Participants With TEAEs-leading to Discontinuation Stage 2 PK Phase (Periods 1 and 2 Only)

Safety Population comprised of all participants who received any amount of niraparib during the Stage 3 PK Phase of the study.

Spots Global Cancer Trial Database for Crossover Study to Assess the Relative Bioavailability and Bioequivalence of Niraparib Tablet Compared to Niraparib Capsule

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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