Ovarian Neoplasms, Platinum Sensitive Ovarian Cancer
Conditions
Keywords
ovarian cancer, platinum sensitive, gBRCAmut, BRCA, high-grade serous histology, PARP inhibitor
Brief summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values. The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).
Interventions
DRUGActive comparator: Niraparib
Niraparib vs placebo 2:1 ratio
DRUGplacebo
Sponsors
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
US Oncology Research
Sarah Cannon
Cooperative Ovarian Cancer Group (COGI)
Facing Our Risk of Cancer Empowered
Tesaro, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older, female, any race * Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer * High grade (or grade 3) serous histology or known to have gBRCAmut * Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease) * Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen * ECOG 0-1 * Adequate bone marrow, kidney and liver function
Exclusion criteria
* Known hypersensitivity to the components of niraparib * Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated) * Symptomatic uncontrolled brain metastasis * Is pregnant or breast feeding * Immunocompromised patients * Known active hepatic disease * Prior treatment with a known PARP inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) | From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days | PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. |
| Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+) | From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days | PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. |
| Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation | From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days | PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation | From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days | Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment |
| Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA) | From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days | Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study. |
| Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation | From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days | Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study. |
| Overall Survival in Cohort With Germline BRCA Mutation (gBRCA) | From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days | Overall survival was defined as the date of randomization to the date of death by any cause. |
| Overall Survival in Cohort With No Germline BRCA Mutation | From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days | Overall survival was defined as the date of randomization to the date of death by any cause. |
| Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days | TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death. |
| Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation | From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days | TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2 | Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 | Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6 | Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression | Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2 | Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4 | Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6 | Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days) | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression | Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days | Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 | Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4 | Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6 | Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression | Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2 | Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4 | Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6 | Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days) | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression | Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days | EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | At Baseline | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). Baseline was latest non-missing pre-dose assessment on or before randomization date. |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | At Cycle 2 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | At Cycle 4 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | At Cycle 6 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Up to 7 years, 7 months and 4 days | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | At Baseline | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). Baseline was latest non-missing pre-dose assessment on or before randomization date. |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | At Cycle 2 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | At Cycle 4 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | At Cycle 6 (Each cycle was of 28 days) | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Up to 7 years, 7 months and 4 days | A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). |
| Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study | Up to 7 years, 7 months and 4 days | This will never be analyzed since the data for the candidate companion BRAC analysis diagnostic test was not collected which was to be compared with centralized BRCA mutation test used in this study. |
| Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study | Up to 7 years, 7 months and 4 days | This will never be analyzed since the data for the candidate companion HRD diagnostic test was not collected which was to be compared with HRD test used in this study. |
| Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Up to 7 years, 7 months and 6 days | An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. Data presented for this outcome measure is based on the data cut-off date of 31-March-2021, which aligns with the time of the study unblinding. |
| Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | Up to 8 months, 26 days | An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. The data is presented for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021 |
| Number of Participants With Non-serious AEs and SAEs in FE Sub-study | Up to 2 years, 3 months and 11 days | An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. |
| Number of Participants With Non-serious AEs and SAEs in QTc Sub-study | Up to 5 years 10 months and 22 days | An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. |
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study) | Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose | Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib. |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study) | Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose | Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib. |
| Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days | The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death. |
| Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study) | Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose | Blood samples were collected at indicated time points to analyze the tmax of niraparib. |
| Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study) | Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose | Blood samples were collected at indicated time points to analyze the t1/2 of niraparib. |
| Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds | At Baseline (Cycle 1 Day 1, each cycle was of 28 days) | 12-lead electrocardiogram was obtained at indicated time points using an automated electrocardiogram machine that measured QTcF interval. The number of participants with maximum post-Baseline ECG value exceeding the following limits have been reported: QTcF interval \>450 and \<= 480 milliseconds (msec) and \>500 msec. |
| Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study) | Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose | Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib. |
| Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation | From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days | The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death |
| Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) | From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days | Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment |
Countries
Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Norway, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
This was a randomized, double-blind study conducted to analyze maintenance with niraparib versus placebo in participants with ovarian cancer.
Pre-assignment details
A total of 596 participants were enrolled in the study. The results presented are based on the data cut-off date of 31 March 2021 (which aligns with the time of the study unblinding) and the post-unblinding safety data until the end of study (01-April-2021 to 26-December-2021).
Participants by arm
| Arm | Count |
|---|---|
| gBRCA Niraparib Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression. | 138 |
| gBRCA Placebo Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression. | 65 |
| Non-gBRCA Niraparib Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression. | 234 |
| Non-gBRCA Placebo Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression | 116 |
| FE Sub-study: Fasted/Fed Participants received a single dose of 3x100 mg capsules of niraparib administered orally following a minimum 10-hour overnight fast in Period 1 followed by 300 mg capsules of niraparib administered orally as single dose in fed condition (high-fat meal) in Period 2. There was a washout period of 7 days between treatment periods. | 8 |
| FE Sub-study: Fed/Fasted Participants received single dose of 3x100 mg capsules of niraparib administered orally following a high-fat meal in Period 1 followed by 3x100 mg capsules of niraparib administered orally as single dose in fasted condition in Period 2. There was a washout period of 7 days between treatment periods. | 9 |
| QTc Sub-study: Niraparib Participants received Niraparib 300 mg once daily orally. | 26 |
| Total | 596 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FE Sub-study, Period1 (Day1) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| FE Sub-study, Washout 1 (Up to Day 7) | Transferred to Other Arm/Group | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study PSU (Up to 8months, 26days) | Other reasons | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 1 |
| Main Study PSU (Up to 8months, 26days) | Subject Moved to Rollover Study | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 9 | 0 |
| Main Study PSU (Up to 8months, 26days) | Subject Unblinded by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 | 8 | 18 | 12 |
| Main Study PSU (Up to 8months, 26days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Death | 72 | 29 | 146 | 68 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Disease progression | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Lost to Follow-up | 7 | 2 | 5 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Ongoing at the time of analysis | 22 | 8 | 31 | 13 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Other reasons | 5 | 3 | 8 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Subject unblinded by sponsor | 12 | 12 | 15 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Upto 7years 7months 6 Days) | Withdrawal by Subject | 20 | 11 | 29 | 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| QTcSub-study(Upto 5 Year,10 Month,22day) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| QTcSub-study(Upto 5 Year,10 Month,22day) | Other Reasons | 0 | 0 | 0 | 0 | 0 | 0 | 17 | 0 | 0 | 0 | 0 |
| QTcSub-study(Upto 5 Year,10 Month,22day) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | gBRCA Niraparib | gBRCA Placebo | Non-gBRCA Niraparib | Non-gBRCA Placebo | FE Sub-study: Fasted/Fed | FE Sub-study: Fed/Fasted | QTc Sub-study: Niraparib | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 28 Participants | 16 Participants | 104 Participants | 47 Participants | 3 Participants | 4 Participants | 10 Participants | 212 Participants |
| Age, Customized Between 18 and 64 years | 110 Participants | 49 Participants | 130 Participants | 69 Participants | 5 Participants | 5 Participants | 16 Participants | 384 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 10 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 20 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 11 Participants | 6 Participants | 19 Participants | 10 Participants | 0 Participants | 0 Participants | 0 Participants | 46 Participants |
| Race/Ethnicity, Customized White | 123 Participants | 55 Participants | 201 Participants | 101 Participants | 6 Participants | 9 Participants | 21 Participants | 516 Participants |
| Sex: Female, Male Female | 138 Participants | 65 Participants | 234 Participants | 116 Participants | 8 Participants | 9 Participants | 26 Participants | 596 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 72 / 136 | 29 / 65 | 146 / 231 | 68 / 114 | 0 / 16 | 0 / 16 | 5 / 26 | 0 / 22 | 0 / 8 | 0 / 31 | 0 / 13 |
| other Total, other adverse events | 136 / 136 | 62 / 65 | 231 / 231 | 110 / 114 | 4 / 16 | 6 / 16 | 24 / 26 | 0 / 22 | 0 / 8 | 0 / 31 | 0 / 13 |
| serious Total, serious adverse events | 51 / 136 | 9 / 65 | 76 / 231 | 20 / 114 | 1 / 16 | 0 / 16 | 12 / 26 | 0 / 22 | 0 / 8 | 0 / 31 | 0 / 13 |
Outcome results
Primary
Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA)
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days
Population: Intent-to-treat population was defined as all randomized participants with participants analyzed according to the study drug assigned via randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) | 21 months |
| gBRCA Placebo | Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer Gene (BRCA) Mutation (gBRCA) | 5.5 months |
p-value: <0.000195% CI: [0.173, 0.41]Log Rank
Primary
Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+) | 12.9 months |
| gBRCA Placebo | Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+) | 3.8 months |
p-value: <0.000195% CI: [0.243, 0.586]Log Rank
Primary
Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation
PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time frame: From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation | 9.3 Months |
| gBRCA Placebo | Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation | 3.9 Months |
p-value: <0.000195% CI: [0.338, 0.607]Log Rank
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib.
Time frame: Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Population: Pharmacokinetic population consisted of all participants who received at least one dose of study drug, with sufficient data available to calculate parameters. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study) | 29016.1 Nanograms*hour per milliliter | Standard Deviation 18405.23 |
| gBRCA Placebo | Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-infinity]) Following Administration of Niraparib (FE Sub-study) | 31194 Nanograms*hour per milliliter | Standard Deviation 16894.88 |
90% CI: [0.997, 1.216]
Secondary
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Population: Pharmacokinetic population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study) | 28638.1 Nanograms*hour per milliliter | Standard Deviation 17911.86 |
| gBRCA Placebo | Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-last]) Following Administration of Niraparib (FE Sub-study) | 27186.4 Nanograms*hour per milliliter | Standard Deviation 14111.37 |
90% CI: [0.978, 1.166]
Secondary
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4 | -0.010 Scores on a scale | Standard Deviation 0.1225 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4 | -0.035 Scores on a scale | Standard Deviation 0.1156 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6 | 0.002 Scores on a scale | Standard Deviation 0.1116 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6 | -0.004 Scores on a scale | Standard Deviation 0.1463 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression | -0.041 Scores on a scale | Standard Deviation 0.1192 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Post-progression | -0.013 Scores on a scale | Standard Deviation 0.158 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2 | -0.007 Scores on a scale | Standard Deviation 0.1013 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2 | -0.011 Scores on a scale | Standard Deviation 0.1015 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4 | -0.004 Scores on a scale | Standard Deviation 0.1077 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4 | -0.014 Scores on a scale | Standard Deviation 0.087 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6 | 0.005 Scores on a scale | Standard Deviation 0.1097 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6 | -0.011 Scores on a scale | Standard Deviation 0.0949 |
Secondary
Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression | -0.047 Scores on a scale | Standard Deviation 0.1355 |
| gBRCA Placebo | Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Post-progression | -0.050 Scores on a scale | Standard Deviation 0.1351 |
Secondary
Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2
EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: no problems (Level 1), slight problems (Level 2), moderate problems (Level 3), severe problems (Level 4), and extreme problems (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 | -0.008 Scores on a scale | Standard Deviation 0.1092 |
| gBRCA Placebo | Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 | -0.008 Scores on a scale | Standard Deviation 0.1354 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2 | -0.8 Scores on a scale | Standard Deviation 4.58 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2 | -0.3 Scores on a scale | Standard Deviation 3.19 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 | -0.1 Scores on a scale | Standard Deviation 4.07 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 | -0.3 Scores on a scale | Standard Deviation 3.88 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6 | 0.5 Scores on a scale | Standard Deviation 3.77 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6 | -0.5 Scores on a scale | Standard Deviation 4.27 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression | -0.751 Scores on a scale | Standard Deviation 4.4342 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Post-progression | -1.324 Scores on a scale | Standard Deviation 4.5034 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2 | -1.0 Scores on a scale | Standard Deviation 3.79 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2 | -0.3 Scores on a scale | Standard Deviation 2.84 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4 | -0.7 Scores on a scale | Standard Deviation 4.16 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4 | -0.9 Scores on a scale | Standard Deviation 4.23 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6 | -0.2 Scores on a scale | Standard Deviation 3.76 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6 | -0.9 Scores on a scale | Standard Deviation 3.43 |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression
Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from not at all (0) to very much (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 (severely symptomatic) to 32 (asymptomatic). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression | -2.595 Scores on a scale | Standard Deviation 5.57 |
| gBRCA Placebo | Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Post-progression | -1.801 Scores on a scale | Standard Deviation 4.029 |
Secondary
Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)
Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment
Time frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) | 20.0 Months |
| gBRCA Placebo | Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) | 9.4 Months |
p-value: <0.000195% CI: [0.268, 0.561]Log Rank
Secondary
Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation
Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment
Time frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation | 13.4 Months |
| gBRCA Placebo | Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation | 8.7 Months |
p-value: <0.000195% CI: [0.428, 0.727]Log Rank
Secondary
Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Population: Pharmacokinetic population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study) | 803.7 Nanograms per milliliter | Standard Deviation 403.35 |
| gBRCA Placebo | Maximum Observed Plasma Concentration (Cmax) Following Administration of Niraparib (FE Sub-study) | 582.1 Nanograms per milliliter | Standard Deviation 228.57 |
90% CI: [0.695, 0.886]
Secondary
Number of Participants With Concordance of a Candidate Companion BRAC Analysis Diagnostic Test Compared to the Centralized BRCA Mutation Test Used in This Study
This will never be analyzed since the data for the candidate companion BRAC analysis diagnostic test was not collected which was to be compared with centralized BRCA mutation test used in this study.
Time frame: Up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population.
Secondary
Number of Participants With Concordance of a Candidate Companion HRD Diagnostic Test Compared to the HRD Test Used in This Study
This will never be analyzed since the data for the candidate companion HRD diagnostic test was not collected which was to be compared with HRD test used in this study.
Time frame: Up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population.
Secondary
Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds
12-lead electrocardiogram was obtained at indicated time points using an automated electrocardiogram machine that measured QTcF interval. The number of participants with maximum post-Baseline ECG value exceeding the following limits have been reported: QTcF interval \>450 and \<= 480 milliseconds (msec) and \>500 msec.
Time frame: At Baseline (Cycle 1 Day 1, each cycle was of 28 days)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds | >450 msec | 2 Participants |
| gBRCA Niraparib | Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds | >480 msec | 0 Participants |
| gBRCA Niraparib | Number of Participants With Maximum Post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) Greater Than Pre-specified Thresholds | >500 msec | 0 Participants |
Secondary
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. Data presented for this outcome measure is based on the data cut-off date of 31-March-2021, which aligns with the time of the study unblinding.
Time frame: Up to 7 years, 7 months and 6 days
Population: Safety Population consisted of all participants who ingested any amount of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 136 Participants |
| gBRCA Niraparib | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 51 Participants |
| gBRCA Placebo | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 62 Participants |
| gBRCA Placebo | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 9 Participants |
| Non-gBRCA Niraparib | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 76 Participants |
| Non-gBRCA Niraparib | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 231 Participants |
| Non-gBRCA Placebo | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 20 Participants |
| Non-gBRCA Placebo | Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs) | Non-serious AEs | 110 Participants |
Secondary
Number of Participants With Non-serious AEs and SAEs in FE Sub-study
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.
Time frame: Up to 2 years, 3 months and 11 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs in FE Sub-study | Non-serious AEs | 4 Participants |
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs in FE Sub-study | SAEs | 1 Participants |
| gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs in FE Sub-study | Non-serious AEs | 6 Participants |
| gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs in FE Sub-study | SAEs | 0 Participants |
Secondary
Number of Participants With Non-serious AEs and SAEs in QTc Sub-study
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events.
Time frame: Up to 5 years 10 months and 22 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs in QTc Sub-study | Non-serious AEs | 24 Participants |
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs in QTc Sub-study | SAEs | 12 Participants |
Secondary
Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding)
An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. The data is presented for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021
Time frame: Up to 8 months, 26 days
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | SAEs | 0 Participants |
| gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | Non-serious AEs | 0 Participants |
| gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | SAEs | 0 Participants |
| gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | Non-serious AEs | 0 Participants |
| Non-gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | Non-serious AEs | 0 Participants |
| Non-gBRCA Niraparib | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | SAEs | 0 Participants |
| Non-gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | Non-serious AEs | 0 Participants |
| Non-gBRCA Placebo | Number of Participants With Non-serious AEs and SAEs (Post-study Unblinding) | SAEs | 0 Participants |
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). Baseline was latest non-missing pre-dose assessment on or before randomization date.
Time frame: At Baseline
Population: Intent-to-treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 0-Not at all | 47 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 1-A little bit | 32 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 2-Somewhat | 24 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 3-Quite a bit | 21 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 4-Very much | 9 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 0-Not at all | 80 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 1-A little bit | 28 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 2-Somewhat | 8 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 3-Quite a bit | 14 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 4-Very much | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 2-Somewhat | 6 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 0-Not at all | 26 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 0-Not at all | 37 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 1-A little bit | 12 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 4-Very much | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 2-Somewhat | 9 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 1-A little bit | 13 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 3-Quite a bit | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Hands, 3-Quite a bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Baseline | Feet, 4-Very much | 6 Participants |
p-value: 0.7969Pearson's Chi-squared test
p-value: 0.8794Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 0-Not at all | 48 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 1-A little bit | 22 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 2-Somewhat | 17 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 4-Very much | 8 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 0-Not at all | 73 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 1-A little bit | 19 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 2-Somewhat | 13 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 3-Quite a bit | 7 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 4-Very much | 3 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 3-Quite a bit | 20 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 0-Not at all | 31 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 0-Not at all | 25 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 4-Very much | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 1-A little bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 1-A little bit | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 2-Somewhat | 15 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 3-Quite a bit | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 3-Quite a bit | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Feet, 4-Very much | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 2 | Hands, 2-Somewhat | 6 Participants |
p-value: 0.2399Pearson's Chi-squared test
p-value: 0.4584Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 4-Very much | 6 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 1-A little bit | 22 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 2-Somewhat | 20 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 3-Quite a bit | 15 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 0-Not at all | 70 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 1-A little bit | 18 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 2-Somewhat | 16 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 3-Quite a bit | 4 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 4-Very much | 2 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 0-Not at all | 47 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 3-Quite a bit | 4 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 0-Not at all | 20 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 1-A little bit | 6 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 1-A little bit | 6 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 3-Quite a bit | 8 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 2-Somewhat | 7 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 2-Somewhat | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Feet, 4-Very much | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 4-Very much | 1 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 4 | Hands, 0-Not at all | 29 Participants |
p-value: 0.8566Pearson's Chi-squared test
p-value: 0.4705Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 0-Not at all | 44 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 1-A little bit | 17 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 2-Somewhat | 13 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 3-Quite a bit | 15 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 4-Very much | 9 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 0-Not at all | 54 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 1-A little bit | 25 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 2-Somewhat | 10 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 3-Quite a bit | 6 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 4-Very much | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 4-Very much | 1 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 0-Not at all | 17 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 0-Not at all | 21 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 1-A little bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 3-Quite a bit | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 2-Somewhat | 7 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 1-A little bit | 8 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 3-Quite a bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Hands, 2-Somewhat | 4 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Cycle 6 | Feet, 4-Very much | 2 Participants |
p-value: 0.8521Pearson's Chi-squared test
p-value: 0.9923Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: Up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 0-Not at all | 31 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 1-A little bit | 20 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 3-Quite a bit | 15 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 4-Very much | 7 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 0-Not at all | 44 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 1-A little bit | 18 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 2-Somewhat | 8 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 3-Quite a bit | 7 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 4-Very much | 3 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 2-Somewhat | 7 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 0-Not at all | 26 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 0-Not at all | 15 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 4-Very much | 0 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 1-A little bit | 9 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 2-Somewhat | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 1-A little bit | 4 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 3-Quite a bit | 7 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 3-Quite a bit | 4 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Feet, 4-Very much | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With Germline BRCA at Post-progression | Hands, 2-Somewhat | 3 Participants |
p-value: 0.9997Pearson's Chi-squared test
p-value: 0.3518Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit). Baseline was latest non-missing pre-dose assessment on or before randomization date.
Time frame: At Baseline
Population: Intent-to-treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 0-Not at all | 71 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 1-A little bit | 58 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 2-Somewhat | 37 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 3-Quite a bit | 43 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 4-Very much | 18 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 0-Not at all | 120 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 1-A little bit | 56 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 2-Somewhat | 28 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 3-Quite a bit | 15 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 4-Very much | 8 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 4-Very much | 2 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 0-Not at all | 40 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 3-Quite a bit | 11 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 1-A little bit | 26 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 1-A little bit | 37 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 2-Somewhat | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 0-Not at all | 48 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 3-Quite a bit | 21 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Hands, 2-Somewhat | 12 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Baseline | Feet, 4-Very much | 9 Participants |
p-value: 0.9367Pearson's Chi-squared test
p-value: 0.2502Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 2 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 0-Not at all | 69 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 1-A little bit | 39 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 2-Somewhat | 30 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 3-Quite a bit | 34 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 4-Very much | 9 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 0-Not at all | 100 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 1-A little bit | 38 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 2-Somewhat | 20 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 3-Quite a bit | 17 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 4-Very much | 4 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 2-Somewhat | 19 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 0-Not at all | 32 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 0-Not at all | 44 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 1-A little bit | 17 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 4-Very much | 3 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 2-Somewhat | 12 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 1-A little bit | 24 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 3-Quite a bit | 18 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Hands, 3-Quite a bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 2 | Feet, 4-Very much | 8 Participants |
p-value: 0.5037Pearson's Chi-squared test
p-value: 0.164Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 4 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 3-Quite a bit | 20 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 1-A little bit | 29 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 2-Somewhat | 34 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 4-Very much | 9 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 2-Somewhat | 14 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 1-A little bit | 37 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 3-Quite a bit | 14 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 0-Not at all | 89 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 4-Very much | 6 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 0-Not at all | 54 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 4-Very much | 1 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 1-A little bit | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 2-Somewhat | 17 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 3-Quite a bit | 11 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 4-Very much | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 0-Not at all | 43 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 1-A little bit | 21 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Feet, 0-Not at all | 31 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 2-Somewhat | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 4 | Hands, 3-Quite a bit | 3 Participants |
p-value: 0.9599Pearson's Chi-squared test
p-value: 0.247Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: At Cycle 6 (Each cycle was of 28 days)
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 3-Quite a bit | 18 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 4-Very much | 5 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 0-Not at all | 68 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 1-A little bit | 30 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 2-Somewhat | 13 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 3-Quite a bit | 9 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 4-Very much | 3 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 0-Not at all | 43 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 1-A little bit | 29 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 2-Somewhat | 30 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 2-Somewhat | 11 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 3-Quite a bit | 9 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 3-Quite a bit | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 4-Very much | 5 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 0-Not at all | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 0-Not at all | 29 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 4-Very much | 0 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 1-A little bit | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Feet, 1-A little bit | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Cycle 6 | Hands, 2-Somewhat | 6 Participants |
p-value: 0.5921Pearson's Chi-squared test
p-value: 0.7459Pearson's Chi-squared test
Secondary
Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression
A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of not at all (0) to very much (4). There are 2 items that ask if the participant's feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant's QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (not at all) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (a little bit).
Time frame: Up to 7 years, 7 months and 4 days
Population: Intent-to-treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 4-Very much | 3 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 1-A little bit | 45 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 2-Somewhat | 23 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 3-Quite a bit | 19 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 4-Very much | 5 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 0-Not at all | 88 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 1-A little bit | 35 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 2-Somewhat | 13 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 3-Quite a bit | 7 Participants |
| gBRCA Niraparib | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 0-Not at all | 57 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 3-Quite a bit | 10 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 0-Not at all | 32 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 0-Not at all | 48 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 1-A little bit | 12 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 2-Somewhat | 9 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 2-Somewhat | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 1-A little bit | 15 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 3-Quite a bit | 16 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Hands, 4-Very much | 1 Participants |
| gBRCA Placebo | Number of Participants With Response to Neuropathy Questionnaire in Cohort With no Germline BRCA at Post-progression | Feet, 4-Very much | 8 Participants |
p-value: 0.0259Pearson's Chi-squared test
p-value: 0.2798Pearson's Chi-squared test
Secondary
Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)
Overall survival was defined as the date of randomization to the date of death by any cause.
Time frame: From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Overall Survival in Cohort With Germline BRCA Mutation (gBRCA) | 40.9 Months |
| gBRCA Placebo | Overall Survival in Cohort With Germline BRCA Mutation (gBRCA) | 38.1 Months |
p-value: 0.35895% CI: [0.606, 1.198]Log Rank
Secondary
Overall Survival in Cohort With No Germline BRCA Mutation
Overall survival was defined as the date of randomization to the date of death by any cause.
Time frame: From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Overall Survival in Cohort With No Germline BRCA Mutation | 31.0 Months |
| gBRCA Placebo | Overall Survival in Cohort With No Germline BRCA Mutation | 34.8 Months |
p-value: 0.686895% CI: [0.813, 1.369]Log Rank
Secondary
Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)
Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.
Time frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA) | 29.9 Months |
| gBRCA Placebo | Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA) | 22.7 Months |
p-value: 0.030295% CI: [0.5, 0.968]Log Rank
Secondary
Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation
Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.
Time frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation | 19.5 Months |
| gBRCA Placebo | Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation | 16.1 Months |
p-value: 0.074895% CI: [0.627, 1.022]Log Rank
Secondary
Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the t1/2 of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Population: Pharmacokinetic population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| gBRCA Niraparib | Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study) | 50.5 Hour | Standard Deviation 17.87 |
| gBRCA Placebo | Terminal Elimination Half-life (t1/2) Following Administration of Niraparib (FE Sub-study) | 47.9 Hour | Standard Deviation 17.54 |
Secondary
Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)
The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.
Time frame: From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | 19.1 Months |
| gBRCA Placebo | Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | 8.6 Months |
p-value: 0.000595% CI: [0.412, 0.783]Log Rank
Secondary
Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation
The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death
Time frame: From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation | 12.4 Months |
| gBRCA Placebo | Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation | 7.4 Months |
p-value: <0.000195% CI: [0.454, 0.74]Log Rank
Secondary
Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study)
Blood samples were collected at indicated time points to analyze the tmax of niraparib.
Time frame: Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose
Population: Pharmacokinetic population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study) | 3.1 Hour |
| gBRCA Placebo | Time to Reach Maximum (Tmax) Following Administration of Niraparib (FE Sub-study) | 6.1 Hour |
Secondary
Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)
TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Time frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | 29.7 Months |
| gBRCA Placebo | Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) | 19.6 Months |
p-value: 0.006195% CI: [0.451, 0.878]Log Rank
Secondary
Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation
TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.
Time frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| gBRCA Niraparib | Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation | 20.3 Months |
| gBRCA Placebo | Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation | 16.7 Months |
p-value: 0.167495% CI: [0.654, 1.077]Log Rank