Trial Outcomes & Findings for A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) (NCT NCT01891344)

Last Updated: 2023-06-12

Results Overview

The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

491 participants

Primary outcome timeframe

Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Results posted on

2023-06-12

Participant Flow

491 subjects were recruited from 64 sites across 6 countries.

Participant milestones

Participant milestones
Measure	Part 1: tBRCA Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.
Overall Study STARTED	40	82	70	12	84	73	107	23
Overall Study COMPLETED	34	80	70	11	80	72	107	23
Overall Study NOT COMPLETED	6	2	0	1	4	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: tBRCA Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 1: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.
Overall Study Ongoing	6	2	0	1	4	1	0	0

Baseline Characteristics

Overall participant count is separated into Part 1 and Part 2 patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	tBRCA n=124 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Non-tBRCA LOH+ n=155 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Non-tBRCA LOH- n=177 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Non-tBRCA LOH Unknown n=35 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Total n=491 Participants Total of all reporting groups
Age, Continuous Part 1	58.5 years n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	65 years n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	65 years n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	69.5 years n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	64.5 years n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Age, Continuous Part 2	60.5 years n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	61 years n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	64 years n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	62 years n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	63 years n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Sex: Female, Male Part 1 · Female	40 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	82 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	70 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	12 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	204 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Sex: Female, Male Part 1 · Male	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Sex: Female, Male Part 2 · Female	84 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	73 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	107 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	23 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	287 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Sex: Female, Male Part 2 · Male	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · American Indian or Alaska Native	1 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · Asian	3 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	4 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	13 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · Native Hawaiian or Other Pacific Islander	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · Black or African American	1 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · White	33 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	67 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	56 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	10 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	166 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · More than one race	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 1 · Unknown or Not Reported	2 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	9 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	8 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	19 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · American Indian or Alaska Native	1 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · Asian	5 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	4 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	14 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · Native Hawaiian or Other Pacific Islander	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · Black or African American	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · White	59 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	46 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	82 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	18 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	205 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · More than one race	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Race (NIH/OMB) Part 2 · Unknown or Not Reported	19 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	22 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	19 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	65 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 0	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 1	17 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	45 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	47 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	10 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	119 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 2	14 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	21 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	16 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	52 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 3	4 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	13 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	6 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	24 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 4	4 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · 5	1 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	3 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 1 · >5	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 0	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 1	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 2	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 3	52 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	44 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	73 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	17 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	186 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 4	32 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	28 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	31 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	6 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	97 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · 5	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Chemotherapy Regimens Part 2 · >5	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 1 · 0	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 1 · 1	17 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	45 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	47 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	10 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	119 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 1 · 2	15 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	25 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	16 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	57 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 1 · 3	6 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	10 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	6 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	23 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 1 · >3	2 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	5 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 2 · 0	0 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 2 · 1	2 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	4 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	7 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	3 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	16 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 2 · 2	34 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	31 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	55 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	7 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	127 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 2 · 3	40 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	36 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	44 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	12 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	132 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Number of Prior Platinum Regimens Part 2 · >3	8 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	12 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 1 · Refractory	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 1 · Resistant	0 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	0 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	1 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	2 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 1 · Sensitive	40 Participants n=40 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	81 Participants n=82 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	70 Participants n=70 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	11 Participants n=12 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	202 Participants n=204 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 2 · Refractory	12 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	14 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	18 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	4 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	48 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 2 · Resistant	41 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	46 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	56 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	15 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	158 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.
Platinum Sensitivity Status Part 2 · Sensitive	31 Participants n=84 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	13 Participants n=73 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	33 Participants n=107 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	4 Participants n=23 Participants • Overall participant count is separated into Part 1 and Part 2 patients.	81 Participants n=287 Participants • Overall participant count is separated into Part 1 and Part 2 patients.

PRIMARY outcome

Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Population: Safety population by HRD subgroups: Consists of all Part 1 patients who received at least one dose of rucaparib.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=40 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=82 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=70 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=12 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)	388 Days Interval 273.0 to 448.0	174 Days Interval 158.0 to 231.0	160 Days Interval 110.0 to 188.0	223 Days Interval 55.0 to 499.0	—	—	—	—

PRIMARY outcome

Population: Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=84 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=73 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=107 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=23 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)	31.0 percentage of participants Interval 21.3 to 42.0	6.8 percentage of participants Interval 2.3 to 15.3	5.6 percentage of participants Interval 2.1 to 11.8	13.0 percentage of participants Interval 2.8 to 33.6	—	—	—	—

SECONDARY outcome

Population: Safety population by HRD subgroups: Consist of all Part 1 patients who received at least one dose of rucaparib

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=40 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=82 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=70 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=12 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)	80.0 percentage of participants Interval 64.4 to 90.9	28.0 percentage of participants Interval 18.7 to 39.1	10.0 percentage of participants Interval 4.1 to 19.5	33.3 percentage of participants Interval 9.9 to 65.1	—	—	—	—

SECONDARY outcome

Population: Safety population by HRD subgroups: Consist of all Part 1 and Part 2 patients who received at least one dose of rucaparib.

The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=40 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=82 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=70 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=12 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA n=84 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ n=73 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- n=107 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown n=23 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria	87.5 percentage of patients Interval 73.2 to 95.8	46.3 percentage of patients Interval 35.3 to 57.7	21.4 percentage of patients Interval 12.5 to 32.9	50.0 percentage of patients Interval 21.1 to 78.9	54.8 percentage of patients Interval 43.5 to 65.7	12.3 percentage of patients Interval 5.8 to 22.1	13.1 percentage of patients Interval 7.3 to 21.0	30.4 percentage of patients Interval 13.2 to 52.9

SECONDARY outcome

Population: Efficacy population by HRD subgroups. The overall number of patients analyzed includes only patients with confirmed RECIST CR or PR.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=32 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=23 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=7 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=4 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA n=26 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ n=5 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- n=6 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown n=3 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Duration of Response Per RECIST v1.1	281 Days Interval 194.0 to 393.0	329 Days Interval 174.0 to 451.0	169 Days Interval 141.0 to 260.0	225 Days Interval 100.0 to 1454.0	176 Days Interval 169.0 to 312.0	282 Days Interval 111.0 to The upper limit of the confidence interval is not estimated due to insufficient number of participants with events.	314 Days Interval 169.0 to The upper limit of the confidence interval is not estimated due to insufficient number of participants with events.	181 Days Interval 169.0 to 224.0

SECONDARY outcome

Population: Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=84 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=73 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=107 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=23 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)	223 Days Interval 188.0 to 275.0	57 Days Interval 54.0 to 112.0	113 Days Interval 63.0 to 165.0	110 Days Interval 56.0 to 154.0	—	—	—	—

SECONDARY outcome

Timeframe: All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

Population: Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=84 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=73 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- n=107 Participants Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown n=23 Participants Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Overall Survival (Part 2 of Study)	22.7 Months Interval 16.7 to 28.6	14.7 Months Interval 10.8 to 19.8	13.3 Months Interval 9.1 to 16.0	14.1 Months Interval 7.4 to 20.1	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

Population: All Part 1 and Part 2 patients with at least one PK sample collected

Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.

Outcome measures

Outcome measures
Measure	Part 1: tBRCA n=196 Participants Patients with a deleterious BRCA mutation detected in their tumor.	Part 1: Non-tBRCA LOH+ n=267 Participants Patients without a BRCA mutation in their tumor, but have high LOH.	Part 1: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 1: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Part 2: tBRCA Patients with a deleterious BRCA mutation detected in their tumor.	Part 2: Non-tBRCA LOH+ Patients without a BRCA mutation in their tumor, but have high LOH.	Part 2: Non-tBRCA LOH- Patients without a BRCA mutation in their tumor, but have low LOH.	Part 2: Non-tBRCA LOH Unknown Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Steady State Trough (Cmin) Level Rucaparib Concentrations Cycle 1 Day 15	2020.76 ng/mL Standard Deviation 1145.164	2276.37 ng/mL Standard Deviation 1587.586	—	—	—	—	—	—
Steady State Trough (Cmin) Level Rucaparib Concentrations Cycle 2 Day 1	1652.27 ng/mL Standard Deviation 935.503	1689.83 ng/mL Standard Deviation 1039.953	—	—	—	—	—	—
Steady State Trough (Cmin) Level Rucaparib Concentrations Cycle 3 Day 1	1557.32 ng/mL Standard Deviation 952.903	1552.09 ng/mL Standard Deviation 1054.346	—	—	—	—	—	—
Steady State Trough (Cmin) Level Rucaparib Concentrations Cycle 4 Day 1	1530.41 ng/mL Standard Deviation 765.940	1629.14 ng/mL Standard Deviation 1026.999	—	—	—	—	—	—

Adverse Events

Part 1 Overall

Serious events: 54 serious events

Other events: 203 other events

Deaths: 2 deaths

Part 2 Overall

Serious events: 92 serious events

Other events: 285 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Department

Clovis Oncology, Inc.

Phone: +1 415 409 7220

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Part 1 Overall n=204 participants at risk All patients who participated in Part 1 who received at least one dose of rucaparib	Part 2 Overall n=287 participants at risk All patients who participated in Part 2 who received at least one dose of rucaparib
Blood and lymphatic system disorders Anaemia	5.4% 11/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Febrile neutropenia	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.1% 6/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Granulocytosis	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Neutropenia	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Thrombocytopenia	0.98% 2/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Cardiac disorders Acute coronary syndrome	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Cardiac disorders Cardiac congestive failure	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Cardiac disorders Myocardial infarction	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Cardiac disorders Pericardial effusion	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Congenital, familial and genetic disorders Long QT syndrome congenital	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal distension	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal pain	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.1% 6/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Ascites	0.98% 2/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Colitis	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Constipation	0.98% 2/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	1.0% 3/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Diarrhoea	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Ileus	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Intestinal obstruction	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.1% 6/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Intestinal perforation	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Large intestinal obstruction	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.00% 0/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Nausea	1.5% 3/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.4% 7/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Obstruction gastric	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Rectal haemorrhage	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Small intestinal obstruction	5.4% 11/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.8% 8/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Subileus	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Vomiting	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	3.1% 9/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Asthenia	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	1.4% 4/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders General physical health deterioration	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.4% 7/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Hyperthermia	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Pain	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.70% 2/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Pyrexia	0.49% 1/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	1.4% 4/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Hepatobiliary disorders Hepatic failure	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Hepatobiliary disorders Hepatic haematoma	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Infections and infestations Appendicitis	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Infections and infestations Bacterial pyelonephritis	0.00% 0/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	0.35% 1/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.

Other adverse events
Measure	Part 1 Overall n=204 participants at risk All patients who participated in Part 1 who received at least one dose of rucaparib	Part 2 Overall n=287 participants at risk All patients who participated in Part 2 who received at least one dose of rucaparib
Blood and lymphatic system disorders Anaemia	35.3% 72/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	42.5% 122/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Neutropenia	5.9% 12/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	6.3% 18/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Blood and lymphatic system disorders Thrombocytopenia	11.3% 23/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	15.3% 44/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal distension	20.1% 41/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	10.8% 31/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal pain	30.9% 63/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	31.0% 89/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal pain lower	5.9% 12/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Abdominal pain upper	15.2% 31/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	12.2% 35/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Ascites	5.9% 12/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Constipation	46.6% 95/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	28.2% 81/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Diarrhoea	37.3% 76/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	28.9% 83/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Dry mouth	5.4% 11/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Dyspepsia	11.8% 24/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	7.0% 20/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Flatulence	6.4% 13/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.4% 7/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.4% 11/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	5.2% 15/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Nausea	78.9% 161/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	76.3% 219/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Stomatitis	12.3% 25/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	5.2% 15/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Gastrointestinal disorders Vomiting	45.1% 92/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	43.6% 125/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Asthenia	11.8% 24/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	23.3% 67/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Chills	7.8% 16/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.8% 8/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Fatigue	68.6% 140/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	54.7% 157/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Influenza like illness	5.4% 11/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	2.1% 6/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Oedema peripheral	10.3% 21/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	13.2% 38/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
General disorders Pyrexia	14.2% 29/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	10.8% 31/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Infections and infestations Nasopharyngitis	7.4% 15/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.5% 13/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Infections and infestations Upper respiratory tract infection	13.2% 27/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	3.5% 10/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Infections and infestations Urinary tract infection	18.1% 37/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	11.5% 33/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Alanine aminotransferase increased	40.7% 83/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	29.6% 85/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Aspartate aminotransferase increased	36.3% 74/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	32.1% 92/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Blood alkaline phosphatase increased	9.3% 19/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	8.4% 24/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Blood cholesterol increased	6.9% 14/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.5% 13/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Blood creatinine increased	18.1% 37/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	22.6% 65/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Neutrophil count decreased	9.8% 20/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Platelet count decreased	7.4% 15/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	12.5% 36/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations Weight decreased	20.6% 42/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	10.5% 30/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Investigations White blood cell count decreased	6.4% 13/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	4.2% 12/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Metabolism and nutrition disorders Decreased appetite	41.7% 85/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	38.3% 110/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Metabolism and nutrition disorders Dehydration	7.8% 16/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	7.0% 20/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Metabolism and nutrition disorders Hypokalaemia	8.3% 17/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	6.6% 19/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Metabolism and nutrition disorders Hypomagnesaemia	6.4% 13/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	10.1% 29/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Metabolism and nutrition disorders Hyponatraemia	3.4% 7/204 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.	5.2% 15/287 • Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years. If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.