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A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

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ClinicalTrials.gov Identifier: NCT02655016
Recruitment Status : Active, not recruiting
First Posted : January 13, 2016
Results First Posted : June 11, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborators:
Gynecologic Oncology Group
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Tesaro, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Ovarian Neoplasms
Ovarian Cancer
Interventions Drug: Niraparib
Drug: Placebo
Enrollment 733
Recruitment Details In this double-blind, randomized, placebo-controlled study, participants with stage III or IV ovarian cancer were randomized to receive either niraparib or placebo in 2:1 ratio. The results presented are based on the primary analysis up to month 34. Data collection is still on-going and additional results will be provided after study completion.
Pre-assignment Details A total of 989 participants were screened, of which 256 participants did not meet eligibility criteria. A total of 733 participants were enrolled and randomized in the study, of which 728 participants received study treatment (4 participants were screen failures after randomization and 1 participant withdrew consent before first dose).
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL). Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Period Title: Overall Study
Started 246 487
Received Study Treatment 244 [1] 484 [2]
Ongoing With Treatment in the Study 69 177
Completed 191 [3] 397 [4]
Not Completed 55 90
Reason Not Completed
Disease progression             6             4
Site closed             0             1
Death             30             48
Lost to Follow-up             1             1
Withdrawal by Subject             18             36
[1]
2 participants never received treatment due to screen failure after randomization.
[2]
3 participants never received treatment (2 failed screening & 1 withdrew consent before first dose).
[3]
69 participants are ongoing in the study.
[4]
177 participants are ongoing in the study.
Arm/Group Title Placebo Niraparib Total
Hide Arm/Group Description Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL). Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL). Total of all reporting groups
Overall Number of Baseline Participants 246 487 733
Hide Baseline Analysis Population Description
Baseline characteristics were presented for all randomized participants including 5 randomized participants who never received treatment (4-Screen failure and 1-Withdrew consent).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 246 participants 487 participants 733 participants
61.3  (10.39) 61.1  (10.79) 61.2  (10.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 487 participants 733 participants
Female
246
 100.0%
487
 100.0%
733
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 246 participants 487 participants 733 participants
White
219
  89.0%
436
  89.5%
655
  89.4%
Black
2
   0.8%
10
   2.1%
12
   1.6%
Asian
11
   4.5%
14
   2.9%
25
   3.4%
American Indian or Alaska Native
0
   0.0%
1
   0.2%
1
   0.1%
Native Hawaiian or other Pacific Islander
0
   0.0%
1
   0.2%
1
   0.1%
Unknown
14
   5.7%
25
   5.1%
39
   5.3%
1.Primary Outcome
Title Progression Free Survival
Hide Description Progression free survival was defined as the time from the date of treatment randomization to the date of first documentation of disease progression or death due to any cause in the absence of documented progression, whichever occurs first. It was assessed by the blinded independent central review (BICR). Median and 95% confidence interval (CI) are presented.
Time Frame Up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population comprised of all participants who were randomized into the study.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 246 487
Median (95% Confidence Interval)
Unit of Measure: Months
8.2
(7.3 to 8.5)
13.8
(11.5 to 14.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Niraparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value was calculated based on stratified log-rank test using randomization stratification factors: administration of neoadjuvant chemotherapy, best response to platinum therapy and homologous recombination deficiency (HRD) status.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.502 to 0.755
Estimation Comments If hazard ratio was found to be <1 then niraparib can be considered as superior to placebo.
2.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from the date of randomization to the date of death by any cause. Median and 95% CI are presented for overall survival interim analysis.
Time Frame Up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 246 487
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(25.0 to NA)
30.3 [2] 
(30.3 to NA)
[1]
NA indicates median and 95% CI (upper limit) could not be derived, as <50% of participants experienced the event within the treatment arm.
[2]
NA indicates 95% CI (upper limit) could not be derived, as <75% of participants experienced the event within the treatment arm.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Niraparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1238
Comments p-value was calculated based on stratified log-rank test using randomization stratification factors: administration of neoadjuvant chemotherapy, best response to platinum therapy and HRD status.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.442 to 1.106
Estimation Comments If hazard ratio was found to be <1 then niraparib can be considered as superior to placebo.
3.Secondary Outcome
Title Time to First Subsequent Therapy (TFST)
Hide Description Time to first subsequent therapy was defined as the time from the date of randomization to the date of the first subsequent anti-cancer therapy or death, whichever occurs first. Median and 95% CI are presented.
Time Frame Up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 246 487
Median (95% Confidence Interval)
Unit of Measure: Months
12.0
(10.3 to 13.9)
18.6
(15.8 to 24.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Niraparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments p-value was calculated based on stratified log-rank test using randomization stratification factors: administration of neoadjuvant chemotherapy, best response to platinum therapy and HRD status.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.521 to 0.802
Estimation Comments If hazard ratio was found to be <1 then niraparib can be considered as superior to placebo.
4.Secondary Outcome
Title Progression-Free Survival-2 (PFS2)
Hide Description PFS2 was defined as the time from the date of randomization to the date of progression on the next anti-cancer therapy following study treatment or death by any cause, whichever occurs first. Median and 95% CI are presented.
Time Frame Up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 246 487
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
27.2 [2] 
(25.3 to NA)
[1]
NA indicates median and 95% CI could not be derived, as <25% of participants experienced the event within the treatment arm.
[2]
NA indicates 95% CI (upper limit) could not be derived, as <75% of participants experienced the event within the treatment arm.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Niraparib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2242
Comments p-value was calculated based on stratified log-rank test using randomization stratification factors: administration of neoadjuvant chemotherapy, best response to platinum therapy and HRD status.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.577 to 1.139
Estimation Comments If hazard ratio was found to be <1 then niraparib can be considered as superior to placebo.
5.Secondary Outcome
Title Change From Baseline in Participant Reported Outcome (PRO): Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI)
Hide Description FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants responded to their symptom experience over the past 7 days using a 5-point Likert scale scored from "not at all" (0) to "very much" (4). FOSI score was calculated as (sum of item scores)*8 divided by (number of items answered). The FOSI score ranged from 0 (severely symptomatic) to 32 (asymptomatic). A higher score indicated a better quality of life (QoL). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 240 479
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-0.3  (0.22) -0.4  (0.15)
6.Secondary Outcome
Title Change From Baseline in PRO: European Quality of Life Scale, 5-dimensions, 5-levels of Severity (EQ-5D-5L) Utility Score
Hide Description The EQ-5D-5L is a well-validated general preference-based, health-related QoL instrument. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 243 477
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
0.005  (0.0066) 0.016  (0.0046)
7.Secondary Outcome
Title Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30)
Hide Description EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Five functional scales had total 15 items (physical-5, role-2, cognitive-4, emotional-2, and social-2). Each functional scales score was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher ("better") level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 244 479
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Physical Functioning, n=244,479 Number Analyzed 244 participants 479 participants
2.119  (0.8131) 2.013  (0.5735)
Role Functioning, n=244,479 Number Analyzed 244 participants 479 participants
2.341  (1.2427) 1.590  (0.8810)
Emotional Functioning, n=243,478 Number Analyzed 243 participants 478 participants
-0.011  (1.1218) -0.870  (0.7685)
Cognitive Functioning, n=243,478 Number Analyzed 243 participants 478 participants
-0.020  (1.2105) -0.842  (0.7952)
Social Functioning, n=243,478 Number Analyzed 243 participants 478 participants
5.557  (1.2449) 4.445  (0.8633)
8.Secondary Outcome
Title Change From Baseline in Global Health Status/QoL of EORTC-QLQ-C30
Hide Description EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale (global health status, QoL), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. A global health status/QoL scale had total 2 items. Each global health status/QoL scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 6*100). The global health status/QoL scales range in score from 0 to 100. Higher score represents a higher ("better") level of health status/QoL. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 243 478
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.177  (1.0005) 1.009  (0.6898)
9.Secondary Outcome
Title Change From Baseline in Symptoms Scales and Symptoms Items (Dyspnea, Appetite Loss, Insomnia, Constipation, Diarrhea and Financial Difficulty) of EORTC-QLQ-C30
Hide Description EORTC-QLQ-C30 incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), a global health status/QoL scale, and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulty) assessing additional symptoms commonly reported by participants with cancer. Symptom scale had total 7 items (fatigue-3, pain-2, nausea/vomiting-2). Each symptoms scales and 6 single additional symptoms items score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales and 6 single additional symptoms scales range in score from 0 to 100. Higher score represents a higher ("worse") level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 244 480
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Fatigue, n=243,479 Number Analyzed 243 participants 479 participants
-0.082  (1.2394) 0.085  (0.8363)
Nausea/Vomiting, n=244,479 Number Analyzed 244 participants 479 participants
1.673  (0.7595) 3.115  (0.4828)
Pain, n=244,480 Number Analyzed 244 participants 480 participants
-0.195  (1.2274) 0.765  (1.0166)
Dyspnea, n=244,479 Number Analyzed 244 participants 479 participants
0.644  (1.3592) 1.347  (0.8518)
Insomnia, n=244,479 Number Analyzed 244 participants 479 participants
2.195  (1.9882) 3.478  (1.2791)
Appetite Loss, n=8,30 Number Analyzed 8 participants 30 participants
-0.827  (4.3987) -0.395  (2.3195)
Constipation, n=244,478 Number Analyzed 244 participants 478 participants
-1.147  (1.5793) 6.356  (1.0446)
Diarrhea, n=8,30 Number Analyzed 8 participants 30 participants
9.335  (3.8667) -3.340  (2.0136)
Financial Difficulties, n=243,475 Number Analyzed 243 participants 475 participants
-5.058  (1.2978) -3.356  (0.9276)
10.Secondary Outcome
Title Change From Baseline in Functional Scales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer Module (EORTC-QLQ-OV28)
Hide Description EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/gastrointestinal [GI] symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Functional scales score (body Image and attitude to disease/treatment) was calculated by averaging scores of all scale items and transforming average scores linearly (1 minus [average score minus 1] divided by 3*100). Functional scales score (sexuality) was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the functional scales range in score from 0 to 100. Higher score represents a higher ("better") level of functioning. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to 34 months
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Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 244 475
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Body Image, n=244,475 Number Analyzed 244 participants 475 participants
10.069  (1.4820) 8.488  (1.0138)
Sexuality, n=240,471 Number Analyzed 240 participants 471 participants
3.257  (1.1886) 3.625  (0.8004)
Attitude to disease/Treatment, n=244,475 Number Analyzed 244 participants 475 participants
12.216  (1.3257) 13.660  (0.9309)
11.Secondary Outcome
Title Change From Baseline in Symptoms Scale of EORTC-QLQ-OV28
Hide Description EORTC-QLQ-OV28 is supplement to EORTC-QLQ-C30. It includes 3 functional scales (body image, sexuality, attitude to disease/treatment) and 5 symptom scales/items (abdominal/GI symptoms, peripheral neuropathy, hormonal/menopausal symptoms, other chemotherapy side-effects, and hair loss). Symptoms scales score was calculated by averaging scores of all scale items and transforming average scores linearly ([average score minus 1] divided by 3*100). All of the symptoms scales range in score from 0 to 100. Higher score represents a higher ("worse") level of symptoms. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose).
Time Frame Baseline (Day 1, Pre-dose) and Up to 34 months
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Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 244 481
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Abdominal/GI, n=244,481 Number Analyzed 244 participants 481 participants
0.832  (0.8110) 2.185  (0.5703)
Peripheral Neuropathy, n=244,480 Number Analyzed 244 participants 480 participants
-9.629  (1.3219) -8.217  (0.9295)
Hormonal/Menopausal Symptoms, n=244,480 Number Analyzed 244 participants 480 participants
-2.521  (1.3074) 1.501  (0.8803)
Other Chemotherapy Side Effects, n=244,480 Number Analyzed 244 participants 480 participants
-3.023  (0.8358) -2.219  (0.5581)
Hair Loss, n=242,477 Number Analyzed 242 participants 477 participants
-20.743  (1.3690) -23.363  (0.9821)
12.Other Pre-specified Outcome
Title Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE
Hide Description An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time Frame Up to 34 months
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Hide Analysis Population Description
Safety Population comprised of all participants who received at least 1 dose of study drug. 5 participants (2 participants from Placebo group and 3 participants from Niraparib group) out of 733 participants did not receive any study treatment and thus, were excluded from the Safety Population.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 244 484
Measure Type: Count of Participants
Unit of Measure: Participants
Any non-SAE
223
  91.4%
478
  98.8%
Any SAE
32
  13.1%
156
  32.2%
13.Other Pre-specified Outcome
Title Area Under the Curve (AUC) From 0 to the Last Quantifiable Concentration (AUC[0-last])
Hide Description Blood samples were planned to be collected for assessment of AUC(0-last).
Time Frame Up to 34 months
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Hide Analysis Population Description
ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Arm/Group Title Niraparib
Hide Arm/Group Description:
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Other Pre-specified Outcome
Title Peak Plasma Concentration (Cmax)
Hide Description Blood samples were planned to be collected for assessment of Cmax.
Time Frame Up to 34 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Arm/Group Title Niraparib
Hide Arm/Group Description:
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
15.Other Pre-specified Outcome
Title Number of Participants With Positive HRD Test
Hide Description Number of participants with positive HRD test was planned to be assessed.
Time Frame Up to 34 months
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Hide Analysis Population Description
ITT Population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description:
Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Serious adverse events (SAEs) and non-SAEs were reported from start of study treatment (Day 1) and up to month 34 (primary analysis)
Adverse Event Reporting Description Non-SAEs and SAEs were presented for Safety Population. 5 participants out of 733 participants did not receive any study treatment and thus, were excluded from the Safety Population. The results presented are based on the primary analysis up to month 34. Data collection is still on-going and additional results will be provided after study completion.
 
Arm/Group Title Placebo Niraparib
Hide Arm/Group Description Participants received placebo matching niraparib 300 milligram (mg) (3×100 mg capsules) (fixed dose) once daily (QD) orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received placebo based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kilogram [kg] and Baseline platelet count >=150,000 per microliter [μL]) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL). Participants received niraparib 300 mg (3×100 mg capsules) (fixed dose) QD orally beginning on Day 1 of every cycle (each cycle of 28-days) in a double-blind fashion until a modified starting dose regimen was implemented in protocol amendment. After the protocol amendment, participants received niraparib based upon the participant's Baseline body weight or Baseline platelet count (individualized dose): 300 mg (3×100 mg capsules for participants with a Baseline body weight >=77 kg and Baseline platelet count >=150,000 per μL) or 200 mg (2×100 mg capsules for participants with a Baseline body weight <77 kg or Baseline platelet count <150,000 per μL).
All-Cause Mortality
Placebo Niraparib
Affected / at Risk (%) Affected / at Risk (%)
Total   31/244 (12.70%)      48/484 (9.92%)    
Hide Serious Adverse Events
Placebo Niraparib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/244 (13.11%)      156/484 (32.23%)    
Blood and lymphatic system disorders     
Anaemia  1  0/244 (0.00%)  0 27/484 (5.58%)  28
Febrile neutropenia  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Neutropenia  1  0/244 (0.00%)  0 6/484 (1.24%)  6
Pancytopenia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Thrombocytopenia  1  0/244 (0.00%)  0 59/484 (12.19%)  65
Cardiac disorders     
Sinus tachycardia  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Ventricular tachycardia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Eye disorders     
Retinal detachment  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gastrointestinal disorders     
Abdominal fat apron  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Abdominal pain  1  2/244 (0.82%)  2 1/484 (0.21%)  1
Abdominal pain lower  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Abdominal pain upper  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Diarrhoea  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Enteritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Ileus  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Intestinal obstruction  1  1/244 (0.41%)  1 5/484 (1.03%)  6
Intestinal perforation  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Large intestinal obstruction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Nausea  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Small intestinal obstruction  1  5/244 (2.05%)  5 14/484 (2.89%)  19
Subileus  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Vomiting  1  1/244 (0.41%)  1 1/484 (0.21%)  1
General disorders     
Fatigue  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gait disturbance  1  0/244 (0.00%)  0 1/484 (0.21%)  1
General physical health deterioration  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Pyrexia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Infections and infestations     
Abdominal abscess  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Appendicitis  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Cellulitis  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Enterocolitis infectious  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Infected lymphocele  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Infection  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Influenza  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Lung infection  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Neutropenic sepsis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Pneumonia  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Pneumonia fungal  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Pyelonephritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Skin bacterial infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Urinary tract infection  1  2/244 (0.82%)  2 1/484 (0.21%)  1
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hip fracture  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Intentional overdose  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Overdose  1  3/244 (1.23%)  4 8/484 (1.65%)  10
Postoperative hernia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Transfusion reaction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Wound complication  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Investigations     
Hepatic enzyme increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
International normalised ratio increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neutrophil count decreased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Platelet count decreased  1  0/244 (0.00%)  0 20/484 (4.13%)  25
Metabolism and nutrition disorders     
Decreased appetite  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Invasive ductal breast carcinoma  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Metastases to breast  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Metastases to central nervous system  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Myelodysplastic syndrome  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Papillary thyroid cancer  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Squamous cell carcinoma  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Thyroid cancer  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Nervous system disorders     
Aphasia  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Product Issues     
Device occlusion  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Psychiatric disorders     
Anxiety  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Confusional state  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Depression  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Insomnia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mania  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mental status changes  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Psychotic disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Renal and urinary disorders     
Ureteric stenosis  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Urethral stenosis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Urinary retention  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Pleural effusion  1  0/244 (0.00%)  0 1/484 (0.21%)  3
Pneumonitis  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Pulmonary embolism  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Social circumstances     
Fasting  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Vascular disorders     
Hypertension  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lymphocele  1  1/244 (0.41%)  1 2/484 (0.41%)  2
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Niraparib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   223/244 (91.39%)      478/484 (98.76%)    
Blood and lymphatic system disorders     
Anaemia  1  43/244 (17.62%)  83 306/484 (63.22%)  921
Anaemia macrocytic  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Febrile neutropenia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Haemorrhagic disorder  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Immune thrombocytopenic purpura  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Iron deficiency anaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Leukocytosis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Leukopenia  1  13/244 (5.33%)  27 57/484 (11.78%)  145
Lymphadenitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lymphadenopathy  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Lymphopenia  1  0/244 (0.00%)  0 12/484 (2.48%)  40
Macrocytosis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neutropenia  1  16/244 (6.56%)  32 126/484 (26.03%)  366
Thrombocytopenia  1  9/244 (3.69%)  12 210/484 (43.39%)  549
Cardiac disorders     
Angina pectoris  1  0/244 (0.00%)  0 3/484 (0.62%)  4
Atrial fibrillation  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Cardiac failure  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Conduction disorder  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Coronary artery disease  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Metabolic cardiomyopathy  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Palpitations  1  5/244 (2.05%)  6 39/484 (8.06%)  45
Sinus tachycardia  1  3/244 (1.23%)  5 12/484 (2.48%)  17
Tachyarrhythmia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tachycardia  1  6/244 (2.46%)  6 25/484 (5.17%)  28
Ventricular extrasystoles  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Ear and labyrinth disorders     
Cerumen impaction  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Deafness  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Ear congestion  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Ear discomfort  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Ear haemorrhage  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Ear pain  1  4/244 (1.64%)  4 6/484 (1.24%)  6
Ear pruritus  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Excessive cerumen production  1  0/244 (0.00%)  0 1/484 (0.21%)  1
External ear pain  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Hypoacusis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Meniere's disease  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Motion sickness  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Paraesthesia ear  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Tinnitus  1  4/244 (1.64%)  6 11/484 (2.27%)  11
Vertigo  1  6/244 (2.46%)  7 13/484 (2.69%)  13
Vertigo positional  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vestibular disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Endocrine disorders     
Hyperparathyroidism  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hyperthyroidism  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Hypothyroidism  1  2/244 (0.82%)  2 2/484 (0.41%)  2
Thyroid cyst  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Thyroid mass  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eye disorders     
Age-related macular degeneration  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blepharospasm  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Cataract  1  2/244 (0.82%)  2 2/484 (0.41%)  2
Cataract nuclear  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Conjunctival haemorrhage  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Conjunctivitis allergic  1  1/244 (0.41%)  1 2/484 (0.41%)  3
Diplopia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Dry eye  1  1/244 (0.41%)  1 11/484 (2.27%)  12
Eye disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eye haemorrhage  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Eye oedema  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eye pain  1  1/244 (0.41%)  1 4/484 (0.83%)  5
Eye swelling  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eyelid oedema  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eyelid sensory disorder  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Hypermetropia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lacrimation increased  1  1/244 (0.41%)  1 1/484 (0.21%)  2
Myopia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Ocular discomfort  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Ocular hyperaemia  1  0/244 (0.00%)  0 2/484 (0.41%)  5
Photophobia  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Photopsia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Retinal exudates  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Retinal haemorrhage  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Scleral disorder  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Vision blurred  1  2/244 (0.82%)  2 5/484 (1.03%)  5
Visual acuity reduced  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Visual impairment  1  1/244 (0.41%)  1 5/484 (1.03%)  5
Vitreous floaters  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Gastrointestinal disorders     
Abdominal discomfort  1  11/244 (4.51%)  11 15/484 (3.10%)  19
Abdominal distension  1  30/244 (12.30%)  36 32/484 (6.61%)  36
Abdominal hernia  1  2/244 (0.82%)  2 4/484 (0.83%)  5
Abdominal mass  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Abdominal pain  1  74/244 (30.33%)  102 105/484 (21.69%)  146
Abdominal pain lower  1  13/244 (5.33%)  17 15/484 (3.10%)  16
Abdominal pain upper  1  21/244 (8.61%)  26 41/484 (8.47%)  59
Abdominal tenderness  1  2/244 (0.82%)  2 4/484 (0.83%)  6
Abnormal faeces  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Aerophagia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Anal fissure  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Anal haemorrhage  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Anal incontinence  1  2/244 (0.82%)  2 1/484 (0.21%)  1
Anal pruritus  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Anorectal discomfort  1  2/244 (0.82%)  3 1/484 (0.21%)  1
Aphthous ulcer  1  1/244 (0.41%)  1 5/484 (1.03%)  5
Ascites  1  8/244 (3.28%)  8 3/484 (0.62%)  3
Cheilitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Chronic gastritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Coeliac disease  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Constipation  1  46/244 (18.85%)  52 189/484 (39.05%)  262
Defaecation urgency  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Dental caries  1  1/244 (0.41%)  2 2/484 (0.41%)  2
Diaphragmatic hernia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Diarrhoea  1  55/244 (22.54%)  82 91/484 (18.80%)  132
Diverticulum intestinal  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Dry mouth  1  6/244 (2.46%)  8 40/484 (8.26%)  46
Dyspepsia  1  14/244 (5.74%)  16 34/484 (7.02%)  43
Dysphagia  1  1/244 (0.41%)  1 6/484 (1.24%)  10
Epigastric discomfort  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Eructation  1  3/244 (1.23%)  3 3/484 (0.62%)  3
Faecaloma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Faeces discoloured  1  1/244 (0.41%)  1 2/484 (0.41%)  3
Faeces soft  1  1/244 (0.41%)  1 2/484 (0.41%)  3
Flatulence  1  7/244 (2.87%)  12 17/484 (3.51%)  20
Frequent bowel movements  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Gastric disorder  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Gastritis  1  2/244 (0.82%)  2 5/484 (1.03%)  5
Gastritis erosive  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gastrointestinal disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gastrointestinal haemorrhage  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gastrointestinal motility disorder  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Gastrointestinal pain  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Gastrointestinal sounds abnormal  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Gastrooesophageal reflux disease  1  7/244 (2.87%)  8 25/484 (5.17%)  28
Gingival bleeding  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Gingival pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Glossitis  1  1/244 (0.41%)  2 1/484 (0.21%)  1
Glossodynia  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Haematochezia  1  3/244 (1.23%)  5 3/484 (0.62%)  3
Haemorrhoidal haemorrhage  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Haemorrhoids  1  4/244 (1.64%)  4 5/484 (1.03%)  6
Hiatus hernia  1  2/244 (0.82%)  2 4/484 (0.83%)  4
Intestinal mass  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Intestinal obstruction  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Large intestine polyp  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Lip blister  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Lip disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lip swelling  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Melaena  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Mouth haemorrhage  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Mouth ulceration  1  1/244 (0.41%)  1 4/484 (0.83%)  5
Nausea  1  67/244 (27.46%)  100 278/484 (57.44%)  448
Noninfective gingivitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Odynophagia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Oesophagitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Oral contusion  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Oral dysaesthesia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Oral mucosal blistering  1  0/244 (0.00%)  0 2/484 (0.41%)  3
Oral mucosal discolouration  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Oral pain  1  3/244 (1.23%)  3 7/484 (1.45%)  9
Pancreatic disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Pancreatitis chronic  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Paraesthesia oral  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Proctalgia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Rectal discharge  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Rectal haemorrhage  1  3/244 (1.23%)  3 5/484 (1.03%)  7
Rectal tenesmus  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Regurgitation  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Retching  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Salivary duct stenosis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Salivary gland calculus  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Salivary hypersecretion  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Small intestinal obstruction  1  2/244 (0.82%)  3 1/484 (0.21%)  1
Stomatitis  1  4/244 (1.64%)  7 16/484 (3.31%)  18
Swollen tongue  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Tongue coated  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Tooth disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tooth impacted  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Toothache  1  0/244 (0.00%)  0 6/484 (1.24%)  6
Umbilical hernia  1  3/244 (1.23%)  3 3/484 (0.62%)  3
Vomiting  1  28/244 (11.48%)  34 108/484 (22.31%)  153
General disorders     
Adhesion  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Asthenia  1  31/244 (12.70%)  47 78/484 (16.12%)  138
Axillary pain  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Catheter site bruise  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Catheter site haematoma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Catheter site pain  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Catheter site rash  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Catheter site vesicles  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Chest discomfort  1  3/244 (1.23%)  3 5/484 (1.03%)  5
Chest pain  1  4/244 (1.64%)  4 3/484 (0.62%)  4
Chills  1  3/244 (1.23%)  3 6/484 (1.24%)  7
Cyst  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Discomfort  1  1/244 (0.41%)  1 3/484 (0.62%)  4
Early satiety  1  2/244 (0.82%)  2 4/484 (0.83%)  4
Facial pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Fatigue  1  72/244 (29.51%)  101 168/484 (34.71%)  242
Feeling abnormal  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Feeling hot  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gait disturbance  1  0/244 (0.00%)  0 2/484 (0.41%)  2
General physical health deterioration  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Generalised oedema  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Hernia  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Hernia pain  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Induration  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Influenza like illness  1  11/244 (4.51%)  12 15/484 (3.10%)  22
Injection site reaction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Local swelling  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Malaise  1  0/244 (0.00%)  0 7/484 (1.45%)  7
Mass  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mucosal dryness  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Mucosal inflammation  1  6/244 (2.46%)  10 23/484 (4.75%)  29
Non-cardiac chest pain  1  2/244 (0.82%)  2 13/484 (2.69%)  15
Oedema peripheral  1  11/244 (4.51%)  19 30/484 (6.20%)  35
Pain  1  6/244 (2.46%)  6 16/484 (3.31%)  17
Peripheral swelling  1  4/244 (1.64%)  4 6/484 (1.24%)  6
Pyrexia  1  15/244 (6.15%)  17 41/484 (8.47%)  47
Secretion discharge  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sensation of foreign body  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Suprapubic pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Swelling  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Ulcer  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Unevaluable event  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Vessel puncture site bruise  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vessel puncture site haematoma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hepatobiliary disorders     
Biliary colic  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Biliary dilatation  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hepatic pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hepatic steatosis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Hepatitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hepatitis toxic  1  0/244 (0.00%)  0 1/484 (0.21%)  4
Hyperbilirubinaemia  1  2/244 (0.82%)  2 2/484 (0.41%)  8
Hypertransaminasaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Liver disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Immune system disorders     
Contrast media allergy  1  2/244 (0.82%)  2 1/484 (0.21%)  1
Contrast media reaction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hypersensitivity  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Seasonal allergy  1  5/244 (2.05%)  5 3/484 (0.62%)  3
Infections and infestations     
Abdominal infection  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Acute sinusitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Anal abscess  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Angular cheilitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Arthritis infective  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Bronchitis  1  1/244 (0.41%)  1 12/484 (2.48%)  13
Candida infection  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Catheter site cellulitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Cellulitis  1  1/244 (0.41%)  3 2/484 (0.41%)  2
Clostridium difficile colitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Conjunctivitis  1  1/244 (0.41%)  1 5/484 (1.03%)  7
Cystitis  1  4/244 (1.64%)  4 6/484 (1.24%)  6
Device related infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Diverticulitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Ear infection  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Eye infection  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Folliculitis  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Fungal infection  1  4/244 (1.64%)  5 0/484 (0.00%)  0
Fungal skin infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Furuncle  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Gastric infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gastroenteritis  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Gastroenteritis viral  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Gastrointestinal candidiasis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Genital herpes  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Gingivitis  1  1/244 (0.41%)  3 2/484 (0.41%)  2
Helicobacter gastritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Herpes zoster  1  4/244 (1.64%)  4 5/484 (1.03%)  8
Hordeolum  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Influenza  1  5/244 (2.05%)  5 6/484 (1.24%)  6
Laryngitis  1  1/244 (0.41%)  2 2/484 (0.41%)  2
Localised infection  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Lung infection  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Lymphangitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Mastitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Medical device site infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mucosal infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Nail infection  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Nasopharyngitis  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Onychomycosis  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Ophthalmic herpes simplex  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Oral fungal infection  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Oral herpes  1  3/244 (1.23%)  4 7/484 (1.45%)  10
Oral infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Otitis externa  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Otitis media  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Paronychia  1  1/244 (0.41%)  2 0/484 (0.00%)  0
Pharyngitis  1  0/244 (0.00%)  0 5/484 (1.03%)  6
Pneumonia  1  2/244 (0.82%)  2 8/484 (1.65%)  9
Pyelonephritis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Respiratory tract infection  1  2/244 (0.82%)  2 3/484 (0.62%)  3
Respiratory tract infection viral  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Rhinitis  1  2/244 (0.82%)  2 9/484 (1.86%)  10
Sepsis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Shigella infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sialoadenitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sinusitis  1  7/244 (2.87%)  7 15/484 (3.10%)  27
Skin candida  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Skin infection  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Soft tissue infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tinea pedis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tonsillitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Tooth abscess  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tooth infection  1  0/244 (0.00%)  0 7/484 (1.45%)  9
Tracheitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Upper respiratory tract infection  1  18/244 (7.38%)  22 28/484 (5.79%)  31
Urinary tract infection  1  19/244 (7.79%)  25 44/484 (9.09%)  48
Vaginal infection  1  2/244 (0.82%)  2 3/484 (0.62%)  4
Viral infection  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Viral upper respiratory tract infection  1  25/244 (10.25%)  40 49/484 (10.12%)  55
Vulvitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vulvovaginal candidiasis  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Vulvovaginal mycotic infection  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Injury, poisoning and procedural complications     
Allergic transfusion reaction  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Animal bite  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Arthropod bite  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Bone contusion  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Chest injury  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Compression fracture  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Contusion  1  3/244 (1.23%)  5 22/484 (4.55%)  29
Fall  1  2/244 (0.82%)  2 12/484 (2.48%)  14
Foot fracture  1  2/244 (0.82%)  3 1/484 (0.21%)  1
Head injury  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Humerus fracture  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Incision site pain  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Incision site swelling  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Incisional hernia  1  3/244 (1.23%)  3 0/484 (0.00%)  0
Joint dislocation  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Laceration  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Ligament sprain  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Limb injury  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Mallet finger  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Meniscus injury  1  1/244 (0.41%)  2 1/484 (0.21%)  1
Muscle injury  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Muscle rupture  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Muscle strain  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Post-traumatic pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Postoperative hernia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Postoperative ileus  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Procedural pain  1  3/244 (1.23%)  4 6/484 (1.24%)  6
Procedural site reaction  1  1/244 (0.41%)  2 0/484 (0.00%)  0
Radius fracture  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Rib fracture  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Scar  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Skin abrasion  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Spinal compression fracture  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Stoma complication  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Stoma site discharge  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Stoma site haemorrhage  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Stoma site inflammation  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sunburn  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Tooth fracture  1  0/244 (0.00%)  0 2/484 (0.41%)  3
Upper limb fracture  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Vaccination complication  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vascular access malfunction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Wound  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Wound complication  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Wound evisceration  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Wrist fracture  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Investigations     
Alanine aminotransferase  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Alanine aminotransferase increased  1  15/244 (6.15%)  21 42/484 (8.68%)  67
Amylase increased  1  0/244 (0.00%)  0 3/484 (0.62%)  4
Aspartate aminotransferase  1  1/244 (0.41%)  1 1/484 (0.21%)  2
Aspartate aminotransferase increased  1  10/244 (4.10%)  16 43/484 (8.88%)  78
Bilirubin conjugated increased  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Blood alkaline phosphatase  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Blood alkaline phosphatase increased  1  6/244 (2.46%)  8 42/484 (8.68%)  66
Blood bilirubin increased  1  0/244 (0.00%)  0 7/484 (1.45%)  13
Blood calcium increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood chloride increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood cholesterol increased  1  1/244 (0.41%)  1 4/484 (0.83%)  4
Blood creatine increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood creatinine increased  1  10/244 (4.10%)  12 55/484 (11.36%)  96
Blood glucose decreased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood glucose increased  1  1/244 (0.41%)  1 4/484 (0.83%)  6
Blood lactate dehydrogenase increased  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Blood magnesium decreased  1  0/244 (0.00%)  0 3/484 (0.62%)  4
Blood potassium increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood pressure increased  1  0/244 (0.00%)  0 5/484 (1.03%)  5
Blood sodium decreased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Blood urea increased  1  1/244 (0.41%)  3 4/484 (0.83%)  4
Bone density decreased  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Carbohydrate antigen 125 increased  1  10/244 (4.10%)  11 7/484 (1.45%)  7
Electrocardiogram QT prolonged  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Eosinophil count decreased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Gamma-glutamyltransferase increased  1  2/244 (0.82%)  2 11/484 (2.27%)  21
Haematocrit decreased  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Haemoglobin decreased  1  0/244 (0.00%)  0 5/484 (1.03%)  7
Heart rate increased  1  0/244 (0.00%)  0 9/484 (1.86%)  10
Hepatic enzyme increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Intraocular pressure increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lipase increased  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Lymphocyte count decreased  1  3/244 (1.23%)  4 25/484 (5.17%)  43
Mean cell volume increased  1  0/244 (0.00%)  0 3/484 (0.62%)  4
Monocyte count decreased  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Monocyte count increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neutrophil count decreased  1  5/244 (2.05%)  10 82/484 (16.94%)  207
Neutrophil count increased  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Platelet count decreased  1  3/244 (1.23%)  4 129/484 (26.65%)  338
Platelet count increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Protein total decreased  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Red blood cell count decreased  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Sputum abnormal  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vitamin D decreased  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Weight decreased  1  4/244 (1.64%)  6 20/484 (4.13%)  27
Weight increased  1  19/244 (7.79%)  30 17/484 (3.51%)  24
White blood cell count decreased  1  8/244 (3.28%)  16 74/484 (15.29%)  205
White blood cell count increased  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Metabolism and nutrition disorders     
Cachexia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Cell death  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Decreased appetite  1  20/244 (8.20%)  21 92/484 (19.01%)  112
Dehydration  1  1/244 (0.41%)  1 6/484 (1.24%)  7
Diabetes mellitus  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Glucose tolerance impaired  1  1/244 (0.41%)  2 2/484 (0.41%)  2
Hyperalbuminaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hypercalcaemia  1  1/244 (0.41%)  2 9/484 (1.86%)  14
Hypercholesterolaemia  1  4/244 (1.64%)  4 7/484 (1.45%)  7
Hypercreatininaemia  1  0/244 (0.00%)  0 3/484 (0.62%)  4
Hyperglycaemia  1  6/244 (2.46%)  8 19/484 (3.93%)  28
Hyperkalaemia  1  3/244 (1.23%)  3 6/484 (1.24%)  10
Hypermagnesaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hypernatraemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hyperphosphataemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hyperproteinaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Hypertriglyceridaemia  1  1/244 (0.41%)  1 2/484 (0.41%)  3
Hyperuricaemia  1  1/244 (0.41%)  2 2/484 (0.41%)  2
Hypoalbuminaemia  1  3/244 (1.23%)  6 8/484 (1.65%)  13
Hypocalcaemia  1  1/244 (0.41%)  1 2/484 (0.41%)  4
Hypochloraemia  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Hypoglycaemia  1  2/244 (0.82%)  3 2/484 (0.41%)  2
Hypokalaemia  1  4/244 (1.64%)  4 25/484 (5.17%)  37
Hypomagnesaemia  1  12/244 (4.92%)  18 38/484 (7.85%)  58
Hyponatraemia  1  3/244 (1.23%)  4 19/484 (3.93%)  35
Hypophosphataemia  1  0/244 (0.00%)  0 2/484 (0.41%)  10
Hypoproteinaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Increased appetite  1  3/244 (1.23%)  3 0/484 (0.00%)  0
Iron deficiency  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Magnesium deficiency  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Polydipsia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Type 2 diabetes mellitus  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vitamin D deficiency  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia  1  47/244 (19.26%)  77 85/484 (17.56%)  116
Arthritis  1  4/244 (1.64%)  6 6/484 (1.24%)  6
Arthropathy  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Back pain  1  24/244 (9.84%)  29 64/484 (13.22%)  84
Bone disorder  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Bone lesion  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Bone pain  1  4/244 (1.64%)  6 2/484 (0.41%)  2
Bone swelling  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Bursitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Costochondritis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Exostosis  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Extremity contracture  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Flank pain  1  4/244 (1.64%)  5 7/484 (1.45%)  8
Gouty arthritis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Groin pain  1  3/244 (1.23%)  3 5/484 (1.03%)  5
Haemarthrosis  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Hypercreatinaemia  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Intervertebral disc protrusion  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Joint effusion  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Joint instability  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Joint range of motion decreased  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Joint stiffness  1  4/244 (1.64%)  7 4/484 (0.83%)  4
Joint swelling  1  0/244 (0.00%)  0 7/484 (1.45%)  9
Limb discomfort  1  3/244 (1.23%)  3 1/484 (0.21%)  1
Muscle contracture  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Muscle fatigue  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Muscle spasms  1  14/244 (5.74%)  25 19/484 (3.93%)  24
Muscle tightness  1  2/244 (0.82%)  2 1/484 (0.21%)  1
Muscular weakness  1  3/244 (1.23%)  3 12/484 (2.48%)  15
Musculoskeletal chest pain  1  9/244 (3.69%)  10 12/484 (2.48%)  17
Musculoskeletal discomfort  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Musculoskeletal disorder  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Musculoskeletal pain  1  8/244 (3.28%)  11 12/484 (2.48%)  15
Musculoskeletal stiffness  1  1/244 (0.41%)  4 7/484 (1.45%)  8
Myalgia  1  13/244 (5.33%)  18 36/484 (7.44%)  49
Myalgia intercostal  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neck pain  1  7/244 (2.87%)  9 12/484 (2.48%)  13
Osteoarthritis  1  2/244 (0.82%)  2 8/484 (1.65%)  10
Osteochondrosis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Osteonecrosis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Osteopenia  1  2/244 (0.82%)  2 2/484 (0.41%)  2
Osteoporosis  1  1/244 (0.41%)  1 14/484 (2.89%)  15
Pain in extremity  1  16/244 (6.56%)  20 38/484 (7.85%)  53
Pain in jaw  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Periarthritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Plantar fasciitis  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Psoriatic arthropathy  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Rheumatoid arthritis  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Rotator cuff syndrome  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Scleroderma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sjogren's syndrome  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Soft tissue disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Spinal osteoarthritis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Spinal pain  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Spondylolisthesis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Synovial cyst  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Tendon pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tendonitis  1  2/244 (0.82%)  2 3/484 (0.62%)  3
Tenosynovitis  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tenosynovitis stenosans  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Trigger finger  1  3/244 (1.23%)  4 1/484 (0.21%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acrochordon  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Basal cell carcinoma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Benign breast neoplasm  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Benign neoplasm of skin  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Cancer pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Invasive breast carcinoma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Lipoma  1  1/244 (0.41%)  3 2/484 (0.41%)  2
Seborrhoeic keratosis  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Skin papilloma  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Vaginal neoplasm  1  2/244 (0.82%)  2 0/484 (0.00%)  0
Nervous system disorders     
Amnesia  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Aphasia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Aphonia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Aura  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Balance disorder  1  0/244 (0.00%)  0 6/484 (1.24%)  6
Burning sensation  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Carpal tunnel syndrome  1  3/244 (1.23%)  5 3/484 (0.62%)  3
Cognitive disorder  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Disturbance in attention  1  1/244 (0.41%)  1 4/484 (0.83%)  4
Dizziness  1  26/244 (10.66%)  30 71/484 (14.67%)  96
Dizziness postural  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Dysaesthesia  1  1/244 (0.41%)  1 1/484 (0.21%)  2
Dysgeusia  1  10/244 (4.10%)  13 25/484 (5.17%)  34
Dyskinesia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Facial nerve disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Headache  1  36/244 (14.75%)  46 126/484 (26.03%)  190
Hemiparesis  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Hypoaesthesia  1  6/244 (2.46%)  6 8/484 (1.65%)  12
Loss of consciousness  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Memory impairment  1  5/244 (2.05%)  5 7/484 (1.45%)  7
Mental impairment  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Migraine  1  3/244 (1.23%)  4 4/484 (0.83%)  5
Motor dysfunction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Neuralgia  1  1/244 (0.41%)  1 2/484 (0.41%)  3
Neuropathy peripheral  1  15/244 (6.15%)  18 31/484 (6.40%)  38
Neurotoxicity  1  3/244 (1.23%)  3 1/484 (0.21%)  1
Paraesthesia  1  8/244 (3.28%)  9 11/484 (2.27%)  20
Peripheral motor neuropathy  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Peripheral sensory neuropathy  1  8/244 (3.28%)  10 18/484 (3.72%)  21
Polyneuropathy  1  1/244 (0.41%)  1 3/484 (0.62%)  3
Presyncope  1  3/244 (1.23%)  3 2/484 (0.41%)  3
Radiculopathy  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Restless legs syndrome  1  1/244 (0.41%)  1 4/484 (0.83%)  4
Sciatica  1  3/244 (1.23%)  4 9/484 (1.86%)  10
Seizure  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Sinus headache  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Somnolence  1  0/244 (0.00%)  0 1/484 (0.21%)  2
Speech disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Syncope  1  1/244 (0.41%)  1 5/484 (1.03%)  6
Tension headache  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Transient global amnesia  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Transient ischaemic attack  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Tremor  1  0/244 (0.00%)  0 7/484 (1.45%)  9
Psychiatric disorders     
Agitation  1  1/244 (0.41%)  1 8/484 (1.65%)  11
Anxiety  1  19/244 (7.79%)  24 43/484 (8.88%)  53
Confusional state  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Depressed mood  1  2/244 (0.82%)  2 2/484 (0.41%)  2
Depression  1  10/244 (4.10%)  14 26/484 (5.37%)  28
Dysphoria  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Emotional disorder  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Genito-pelvic pain/penetration disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Hallucination  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Hallucination, olfactory  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Initial insomnia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Insomnia  1  35/244 (14.34%)  37 119/484 (24.59%)  162
Irritability  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Libido decreased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Libido increased  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mania  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Mood swings  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Nervousness  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Nightmare  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Panic attack  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Psychotic disorder  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Restlessness  1  0/244 (0.00%)  0 3/484 (0.62%)  3
Sleep disorder  1  1/244 (0.41%)  1 3/484 (0.62%)  4
Stress  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Suicidal ideation  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Renal and urinary disorders     
Acute kidney injury  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Azotaemia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Bladder discomfort  1  0/244 (0.00%)  0 4/484 (0.83%)  4
Bladder pain  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Bladder spasm  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Chronic kidney disease  1  1/244 (0.41%)  1 2/484 (0.41%)  2
Cystitis interstitial  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Cystitis noninfective  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Dysuria  1  10/244 (4.10%)  11 21/484 (4.34%)  22
Haematuria  1  6/244 (2.46%)  6 5/484 (1.03%)  6
Leukocyturia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Micturition disorder  1  0/244 (0.00%)  0 2/484 (0.41%)  3
Micturition urgency  1  4/244 (1.64%)  4 3/484 (0.62%)  3
Nephritis  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Nephropathy  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Nocturia  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Pollakiuria  1  5/244 (2.05%)  5 11/484 (2.27%)  11
Polyuria  1  1/244 (0.41%)  3 1/484 (0.21%)  1
Proteinuria  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Renal colic  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Renal failure  1  0/244 (0.00%)  0 2/484 (0.41%)  2
Renal pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Urethral pain  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Urinary incontinence  1  1/244 (0.41%)  1 1/484 (0.21%)  1
Urinary retention  1  1/244 (0.41%)  1 0/484 (0.00%)  0
Urinary tract obstruction  1  0/244 (0.00%)  0 1/484 (0.21%)  1
Urinary tract pain  1  1/244 (0.41%)  1 4/484 (0.83%)  4
Urine odour abnormal  1  1/244 (0.41%)  2 2/484 (0.41%)  2