A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01482715
• Collaborator: Foundation Medicine (Industry)
• Enrollment: 136
• Locations: 16
• Arms: 4
• Actual Duration (Months): 90
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate the safety of different doses and dosing regimens of oral rucaparib administered daily to patients with solid tumors.

Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second part of the study is to determine the safety and clinical activity of the RP2D of oral rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or somatic).

Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer; Advanced Solid Tumor With Evidence of Germline or Somatic BRCA	Drug: Rucaparib	Phase 1/Phase 2

Detailed Description

Rucaparib (CO-338; formerly known as PF 01367338 and AG 14699) is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination [HR] DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies.

An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with BRCA1 or BRCA2 mutations. For this study, it is anticipated that rucaparib will promote cell death in the BRCA-deficient tumor cells of ovarian cancer patients with evidence of a germline mutation, thereby limiting tumor progression and providing therapeutic benefit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 136 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor
• Actual Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: May 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 (Phase 1) Rucaparib 40, 80, 160, 300, 500 mg QD and 240, 360, 480, 600, 840 mg BID, for continuous 21-day cycles. Patients in Part 1 were initially treated in a Dose-escalation Evaluation Period (Cycle 1) and could then continue to receive treatment in an optional Treatment-extension Period (Cycle 2 and beyond).	Drug: Rucaparib; Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.; Other Names: CO-338; PF 01367338, AG 14699
Experimental: Part 2A (Phase 2) Rucaparib 600 mg BID for 21-day cycles.	Drug: Rucaparib; Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.; Other Names: CO-338; PF 01367338, AG 14699
Experimental: Part 2B (Phase 2) Rucaparib 600 mg BID for 21-day cycles.	Drug: Rucaparib; Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.; Other Names: CO-338; PF 01367338, AG 14699
Experimental: Part 3 (Phase 2) Rucaparib 600 mg BID for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.	Drug: Rucaparib; Oral tablets administered daily with 8 oz (240 mL) of water on an empty stomach or with food; 21-day cycles of treatment. In Part 1, the initial dose level is 40 mg/day (once a day); doses and dosing frequency(e.g. twice a day or three times a day) will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. Patients enrolled in Part 2 and Part 3 will receive the RP2D for continuous 21-day treatment cycles until disease progression.; Other Names: CO-338; PF 01367338, AG 14699

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate Per RECIST Version 1.1 (Part 2) [Time from first dose to date of progression, up to approximately 8 months]

   The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.

2. Number of Participants With a Dose Limiting Toxicity (DLT) [Cycle 1 Day 1 to Cycle 1 Day 21]

   The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

3. PK Profile of Rucaparib - Cmax (Part 1) [Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days]

   Cmax = maximum concentration following administration of rucaparib

4. PK Profile of Rucaparib - Tmax (Part 1) [Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days]

   Tmax = time to maximum concentration following administration of rucaparib

5. PK Profile of Rucaparib - AUC Last (Part 1) [Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days]

   AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation

Secondary Outcome Measures

1. Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2) [Cycle 1 Day 1 to End of Treatment, up to approximately 51 months]

   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.

2. Duration of Response Per RECIST Version 1.1 (Part 2) [Cycle 1 Day 1 to End of Treatment, up to approximately 48 months]

   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 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.

3. Overall Survival (Part 2B) [Cycle 1 Day 1 to date of death, assessed up to 38 months]

   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 documented event of death will be censored on the date of their last visit.

4. Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3) [Day -7 to Cycle 1 Day 1, or approximately 7 days]

   Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.

5. Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3) [Day -7 to Cycle 1 Day 1, or approximately 7 days]

   Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.

6. Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3) [Day -7 to Cycle 1 Day 1, or approximately 7 days]

   AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.

7. QTcF Value Change From Baseline (Part 1) [Screening to End of Treatment, up to approximately 15 months]

   QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.

Eligibility Criteria

Criteria

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

The following eligibility criteria below pertain to patients enrolling into Part 2B of the study.

Inclusion Criteria:

• Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local laboratory that has received an international or country-specific, quality standards certification)

• Have evidence of measurable disease as defined by RECIST Version 1.1

• Have sufficient archival FFPE tumor tissue available for planned analyses. Archival tissue from the most recently collected biopsy or debulking surgery should be provided, if available.

• Have a histologically confirmed diagnosis of high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer

• Have received at least three prior chemotherapy regimens and have relapsed disease confirmed by radiologic assessment

Exclusion Criteria:

• Active second malignancy, i.e., patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment

1. Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed >6 months prior and/or bone marrow transplant (BMT) >2 years prior to first dose of rucaparib

• Prior treatment with any PARP inhibitor.

• Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.

• Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs 14 days prior to first dose of rucaparib and/or ongoing adverse effects from such treatment > NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent treatment may be permitted with prior advanced approval from Sponsor).

• Hospitalization for bowel obstruction within 3 months prior to enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF	San Francisco	California	United States	94155
2	Sarah Cannon Research Institute	Sarasota	Florida	United States	34232
3	Dana-Farber Cancer Institute (Part 3 only)	Boston	Massachusetts	United States	02215
4	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
5	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
6	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
7	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	MSG 2M9
8	Sheba Medical Center	Ramat Gan		Israel	52621
9	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	632394
10	Hospital Vall d'Hebron	Barcelona		Spain	8035
11	Guy's and St Thomas NHS Foundation Trust	London	England	United Kingdom	SE1 9RT
12	Royal Marsden NHS Foundation Trust	London	England	United Kingdom	SW3 6JJ
13	Imperial College Healthcare	London	England	United Kingdom	W12 0HS
14	Newcastle University	Newcastle Upon Tyne	England	United Kingdom	UK NE7
15	Institution of Cancer Science, University of Glasgow Wolfson Wohl Cancer Research	Glasgow	Scotland	United Kingdom	G61 1QH
16	University College London Cancer Institute	London		United Kingdom	WC1E 6BT

Sponsors and Collaborators

• Clovis Oncology, Inc.
• Foundation Medicine

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 29, 2016
• Statistical Analysis Plan - May 10, 2019

More Information

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT01482715
• Other Study ID Numbers: CO-338-010
• First Posted: Nov 30, 2011
• Last Update Posted: Jan 22, 2021
• Last Verified: Nov 1, 2020

• Keywords provided by Clovis Oncology, Inc.: gBRCA ovarian cancer; platinum sensitive; PARP Inhibitor; Rucaparib; CO-338; PF 01367338; AG 14699; BRCA1; BRCA2; platinum sensitive ovarian cancer; platinum sensitive gBRCA ovarian cancer; gynecological cancer; relapsed disease; homologous recombination deficiency; HRD
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Rucaparib

Study Results

Participant Flow

Recruitment Details	The study was conducted at 15 investigative sites in the United States (6 sites), United Kingdom (5 sites), Spain (1 site), Israel (2 sites), and Canada (1 site).

Arm/Group Title	Rucaparib 40 mg QD (Part 1)	Rucaparib 80 mg QD (Part 1)	Rucaparib 160 mg QD (Part 1)	Rucaparib 300 mg QD (Part 1)	Rucaparib 500 mg QD (Part 1)	Rucaparib 240 mg BID (Part 1)	Rucaparib 360 mg BID (Part 1)	Rucaparib 480 mg BID (Part 1)	Rucaparib 600 mg BID (Part 1)	Rucaparib 840 mg BID (Part 1)	Rucaparib 600 mg BID (Part 2A)	Rucaparib 600 mg BID (Part 2B)	Rucaparib 600 mg BID (Part 3)
Arm/Group Description	Rucaparib 40 mg once a day (QD) for continuous 21-day cycles	Rucaparib 80 mg once a day (QD) for continuous 21-day cycles	Rucaparib 160 mg once a day (QD) for continuous 21-day cycles	Rucaparib 300 mg once a day (QD) for continuous 21-day cycles	Rucaparib 500 mg once a day (QD) for continuous 21-day cycles	Rucaparib 240 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 360 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 480 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 600 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 840 mg twice a day (BID) for continuous 21-day cycles	Rucaparib 600 mg twice a day (BID) for 21-day cycles	Rucaparib 600 mg twice a day (BID) for 21-day cycles	Rucaparib 600 mg twice a day (BID) for 21-day cycles. Patients also received a single administration of 600 mg rucaparib on both Day -7 and Day 1 for assessing the effect of food on PK.
Period Title: Overall Study
STARTED	6	3	4	9	4	3	8	9	7	3	42	12	26
COMPLETED	6	3	4	9	4	3	8	9	7	3	42	12	26
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Rucaparib 40 mg QD (Part 1)	Rucaparib 80 mg QD (Part 1)	Rucaparib 160 mg QD (Part 1)	Rucaparib 300 mg QD (Part 1)	Rucaparib 500 mg QD (Part 1)	Rucaparib 240 mg BID (Part 1)	Rucaparib 360 mg BID (Part 1)	Rucaparib 480 mg BID (Part 1)	Rucaparib 600 mg BID (Part 1)	Rucaparib 840 mg BID (Part 1)	Rucaparib 600 mg BID (Part 2A)	Rucaparib 600 mg BID (Part 2B)	Rucaparib 600 mg BID (Part 3)	Total
Arm/Group Description	Rucaparib 40 mg QD for continuous 21-day cycles	Rucaparib 80 mg QD for continuous 21-day cycles	Rucaparib 160 mg QD for continuous 21-day cycles	Rucaparib 300 mg QD for continuous 21-day cycles	Rucaparib 500 mg QD for continuous 21-day cycles	Rucaparib 240 mg BID for continuous 21-day cycles	Rucaparib 360 mg BID for continuous 21-day cycles	Rucaparib 480 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 840 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID for continuous 21-day cycles	Rucaparib 600 mg BID for continuous 21-day cycles	Total of all reporting groups
Overall Participants	6	3	4	9	4	3	8	9	7	3	42	12	26	136
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.5	46.0	52.0	48.0	29.5	64.0	49.5	46.0	52.0	55.0	56.5	57.5	59.5	57.0
Sex: Female, Male (Count of Participants)
Female	6 100%	3 100%	4 100%	9 100%	2 50%	2 66.7%	7 87.5%	9 100%	7 100%	2 66.7%	42 100%	12 100%	21 80.8%	126 92.6%
Male	0 0%	0 0%	0 0%	0 0%	2 50%	1 33.3%	1 12.5%	0 0%	0 0%	1 33.3%	0 0%	0 0%	5 19.2%	10 7.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	1 11.1%	0 0%	1 33.3%	3 7.1%	0 0%	1 3.8%	7 5.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	2 22.2%	1 25%	0 0%	1 12.5%	0 0%	0 0%	0 0%	3 7.1%	0 0%	2 7.7%	9 6.6%
White	6 100%	3 100%	4 100%	7 77.8%	3 75%	3 100%	6 75%	8 88.9%	7 100%	2 66.7%	35 83.3%	11 91.7%	22 84.6%	117 86%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.4%	0 0%	1 3.8%	2 1.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 8.3%	0 0%	1 0.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate Per RECIST Version 1.1 (Part 2)
Description	The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.
Time Frame	Time from first dose to date of progression, up to approximately 8 months

Outcome Measure Data

Analysis Population Description

Efficacy-Evaluable Population - all Part 2 patients who met eligibility criteria, received at least 1 dose of rucaparib, had measurable tumor lesions at baseline, and had at least 1 post-baseline disease assessment. 2 patients in Part 2A discontinued treatment due to an AE and did not have a post-baseline disease assessment.

Arm/Group Title	Rucaparib 600 mg BID (Part 2A)	Rucaparib 600 mg BID (Part 2B)
Arm/Group Description	Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID for 21-day cycles
Measure Participants	40	12
Count of Participants [Participants]	25 416.7%	7 233.3%

2. Primary Outcome

Title	Number of Participants With a Dose Limiting Toxicity (DLT)
Description	The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.
Time Frame	Cycle 1 Day 1 to Cycle 1 Day 21

Outcome Measure Data

Analysis Population Description

DLT-evaluable population - all patients enrolled into Part 1 of the study who received at least 17 complete days of rucaparib and completed Cycle 1 of treatment, or who experienced a DLT in Cycle 1.

Arm/Group Title	Rucaparib 40 mg QD (Part 1)	Rucaparib 80 mg QD (Part 1)	Rucaparib 160 mg QD (Part 1)	Rucaparib 300 mg QD (Part 1)	Rucaparib 500 mg QD (Part 1)	Rucaparib 240 mg BID (Part 1)	Rucaparib 360 mg BID (Part 1)	Rucaparib 480 mg BID (Part 1)	Rucaparib 600 mg BID (Part 1)	Rucaparib 840 mg BID (Part 1)
Arm/Group Description	Rucaparib 40 mg once a day (QD)	Rucaparib 80 mg once a day (QD)	Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg twice a day (BID)
Measure Participants	6	3	4	9	4	3	8	9	7	3
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rucaparib 600 mg BID (Part 2A), Rucaparib 600 mg BID (Part 2B), Rucaparib 160 mg QD (Part 1), Rucaparib 300 mg QD (Part 1), Rucaparib 500 mg QD (Part 1), Rucaparib 240 mg BID (Part 1), Rucaparib 360 mg BID (Part 1), Rucaparib 480 mg BID (Part 1), Rucaparib 600 mg BID (Part 1), Rucaparib 840 mg BID (Part 1)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	RP2D
	Estimated Value	600
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		A MTD was not established based on observation of DLTs in Cycle 1 of treatment. The 600 mg BID dose was considered to be the maximum dose with an acceptable toxicity profile that could be continuously administered to patients and was selected as the recommended Phase 2 dose (RP2D).

3. Primary Outcome

Title	PK Profile of Rucaparib - Cmax (Part 1)
Description	Cmax = maximum concentration following administration of rucaparib
Time Frame	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Outcome Measure Data

Analysis Population Description

PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 80 mg QD	Rucaparib 160 mg QD	Rucaparib 300 mg QD	Rucaparib 500 mg QD	Rucaparib 240 mg BID	Rucaparib 360 mg BID	Rucaparib 480 mg BID	Rucaparib 600 mg BID	Rucaparib 840 mg BID
Arm/Group Description	Rucaparib 40 mg once a day (QD)	Rucaparib 80 mg once a day (QD)	Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg twice a day (BID)
Measure Participants	3	3	4	3	3	3	8	9	7	3
Day 1 Cmax	120	119	255	700	699	132	603	1090	972	954
Day 15 Cmax	159	180	267	439	1250	783	1220	2480	2330	3030

4. Primary Outcome

Title	PK Profile of Rucaparib - Tmax (Part 1)
Description	Tmax = time to maximum concentration following administration of rucaparib
Time Frame	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Outcome Measure Data

Analysis Population Description

PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 80 mg QD	Rucaparib 160 mg QD	Rucaparib 300 mg QD	Rucaparib 500 mg QD	Rucaparib 240 mg BID	Rucaparib 360 mg BID	Rucaparib 480 mg BID	Rucaparib 600 mg BID	Rucaparib 840 mg BID
Arm/Group Description	Rucaparib 40 mg once a day (QD)	Rucaparib 80 mg once a day (QD)	Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg twice a day (BID)
Measure Participants	3	3	4	3	3	3	8	9	7	3
Day 1 Tmax	2.5	1.5	4	2.5	4	6	3.23	2.5	4	4
Day 15 Tmax	4	2.5	3.75	2.53	4	1.5	3.3	1.51	4	4.04

5. Primary Outcome

Title	PK Profile of Rucaparib - AUC Last (Part 1)
Description	AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation
Time Frame	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Outcome Measure Data

Analysis Population Description

PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 80 mg QD	Rucaparib 160 mg QD	Rucaparib 300 mg QD	Rucaparib 500 mg QD	Rucaparib 240 mg BID	Rucaparib 360 mg BID	Rucaparib 480 mg BID	Rucaparib 600 mg BID	Rucaparib 840 mg BID
Arm/Group Description	Rucaparib 40 mg once a day (QD)	Rucaparib 80 mg once a day (QD)	Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg twice a day (BID)
Measure Participants	3	3	4	3	3	3	8	9	7	3
Day 1 AUC last	915	916	2730	5820	7670	875	4160	6190	6700	5930
Day 15 AUC last	2270	1870	3510	6090	16500	6340	9110	19400	19700	24900

6. Secondary Outcome

Title	Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator (Part 2)
Description	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.
Time Frame	Cycle 1 Day 1 to End of Treatment, up to approximately 51 months

Outcome Measure Data

Analysis Population Description

Safety population: Consist of all Part 2 patients who received at least one dose of rucaparib

Arm/Group Title	Rucaparib 600 mg BID (Part 2A)	Rucaparib 600 mg BID (Part 2B)
Arm/Group Description	Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID for 21-day cycles
Measure Participants	42	12
Median (95% Confidence Interval) [Days]	260	280

7. Secondary Outcome

Title	Duration of Response Per RECIST Version 1.1 (Part 2)
Description	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 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.
Time Frame	Cycle 1 Day 1 to End of Treatment, up to approximately 48 months

Outcome Measure Data

Analysis Population Description

Safety population - all Part 2 patients with confirmed response per investigator.

Arm/Group Title	Rucaparib 600 mg BID (Part 2A)	Rucaparib 600 mg BID (Part 2B)
Arm/Group Description	Rucaparib 600 mg BID for 21-day cycles	Rucaparib 600 mg BID for 21-day cycles
Measure Participants	25	7
Median (95% Confidence Interval) [Days]	270	318

8. Secondary Outcome

Title	Overall Survival (Part 2B)
Description	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 documented event of death will be censored on the date of their last visit.
Time Frame	Cycle 1 Day 1 to date of death, assessed up to 38 months

Outcome Measure Data

Analysis Population Description

Safety population: Consist of all Part 2B patients who received at least one dose of rucaparib

Arm/Group Title	Rucaparib 600 mg BID (Part 2B)
Arm/Group Description	Rucaparib 600 mg BID for 21-day cycles
Measure Participants	12
Median (95% Confidence Interval) [Days]	764

9. Secondary Outcome

Title	Food Effect on PK of Rucaparib - Cmax (Part 1 and Part 3)
Description	Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.
Time Frame	Day -7 to Cycle 1 Day 1, or approximately 7 days

Outcome Measure Data

Analysis Population Description

A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 300 mg QD	Rucaparib 600 mg BID
Arm/Group Description	Rucaparib 40 mg single dose	Rucaparib 300 mg single dose	Rucaparib 600 mg single dose
Measure Participants	3	6	26
Cmax Fasted	57.6	424	585
Cmax Fed	71.1	393	746

10. Secondary Outcome

Title	Food Effect on PK of Rucaparib - Tmax (Part 1 and Part 3)
Description	Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.
Time Frame	Day -7 to Cycle 1 Day 1, or approximately 7 days

Outcome Measure Data

Analysis Population Description

A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 300 mg QD	Rucaparib 600 mg BID
Arm/Group Description	Rucaparib 40 mg single dose	Rucaparib 300 mg single dose	Rucaparib 600 mg single dose
Measure Participants	3	6	26
Tmax Fasted	4	4.09	4.02
Tmax Fed	2.55	5.95	7.83

11. Secondary Outcome

Title	Food Effect on PK of Rucaparib - AUC Last (Part 1 and Part 3)
Description	AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.
Time Frame	Day -7 to Cycle 1 Day 1, or approximately 7 days

Outcome Measure Data

Analysis Population Description

A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib. For the 40 mg and 300 mg arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 300 mg QD	Rucaparib 600 mg BID
Arm/Group Description	Rucaparib 40 mg single dose	Rucaparib 300 mg single dose	Rucaparib 600 mg single dose
Measure Participants	3	6	26
AUC last Fasted	468	5410	7050
AUC last Fed	794	6000	10900

12. Secondary Outcome

Title	QTcF Value Change From Baseline (Part 1)
Description	QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Time Frame	Screening to End of Treatment, up to approximately 15 months

Outcome Measure Data

Analysis Population Description

Safety population: Consist of all Part 1 patients who received at least one dose of rucaparib. One patient in the 40 mg dose group had no Baseline evaluation and was excluded from analyses of change from Baseline.

Arm/Group Title	Rucaparib 40 mg QD	Rucaparib 80 mg QD	Rucaparib 160 mg QD	Rucaparib 300 mg QD	Rucaparib 500 mg QD	Rucaparib 240 mg BID	Rucaparib 360 mg BID	Rucaparib 480 mg BID	Rucaparib 600 mg BID	Rucaparib 840 mg BID
Arm/Group Description	Rucaparib 40 mg once a day (QD)	Rucaparib 80 mg once a day (QD)	Rucaparib 160 mg once a day (QD)	Rucaparib 300 mg once a day (QD)	Rucaparib 500 mg once a day (QD)	Rucaparib 240 mg twice a day (BID)	Rucaparib 360 mg twice a day (BID)	Rucaparib 480 mg twice a day (BID)	Rucaparib 600 mg twice a day (BID)	Rucaparib 840 mg twice a day (BID)
Measure Participants	5	3	4	9	4	3	8	9	7	3
QTcF Change from Baseline <30 msec	5 83.3%	3 100%	4 100%	9 100%	3 75%	3 100%	8 100%	9 100%	7 100%	3 100%
QTcF Change from Baseline ≥30 to <60 msec	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	0 0%	0 0%
QTcF Change from Baseline ≥60 msec	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were reported from the date of first dose of study drug and within 28 days after last dose of study drug. The first patient was dosed in 2012 through study completion in 2017, with an average treatment duration of 173.9 days in Part 1, 331.1 days in Part 2A, 348.2 days in Part 2B, and 198.8 days in Part 3.
Arm/Group Title	Rucaparib 40 mg QD (Part 1)		Rucaparib 80 mg QD (Part 1)		Rucaparib 160 mg QD (Part 1)		Rucaparib 300 mg QD (Part 1)		Rucaparib 500 mg QD (Part 1)		Rucaparib 240 mg BID (Part 1)		Rucaparib 360 mg BID (Part 1)		Rucaparib 480 mg BID (Part 1)		Rucaparib 600 mg BID (Part 1)		Rucaparib 840 mg BID (Part 1)		Rucaparib 600 mg BID (Part 2A)		Rucaparib 600 mg BID (Part 2B)		Rucaparib 600 mg BID (Part 3)
Arm/Group Description	Rucaparib 40 mg QD for 21-day cycles		Rucaparib 80 mg QD for 21-day cycles		Rucaparib 160 mg QD for 21-day cycles		Rucaparib 300 mg QD for 21-day cycles		Rucaparib 500 mg QD for 21-day cycles		Rucaparib 240 mg BID for 21-day cycles		Rucaparib 360 mg BID for 21-day cycles		Rucaparib 480 mg BID for 21-day cycles		Rucaparib 600 mg BID for 21-day cycles		Rucaparib 840 mg BID for 21-day cycles		Rucaparib 600 mg BID for 21-day cycles		Rucaparib 600 mg BID for 21-day cycles		Rucaparib 600 mg BID for 21-day cycles
All Cause Mortality
	Rucaparib 40 mg QD (Part 1)		Rucaparib 80 mg QD (Part 1)		Rucaparib 160 mg QD (Part 1)		Rucaparib 300 mg QD (Part 1)		Rucaparib 500 mg QD (Part 1)		Rucaparib 240 mg BID (Part 1)		Rucaparib 360 mg BID (Part 1)		Rucaparib 480 mg BID (Part 1)		Rucaparib 600 mg BID (Part 1)		Rucaparib 840 mg BID (Part 1)		Rucaparib 600 mg BID (Part 2A)		Rucaparib 600 mg BID (Part 2B)		Rucaparib 600 mg BID (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		1/12 (8.3%)		4/26 (15.4%)
Serious Adverse Events
	Rucaparib 40 mg QD (Part 1)		Rucaparib 80 mg QD (Part 1)		Rucaparib 160 mg QD (Part 1)		Rucaparib 300 mg QD (Part 1)		Rucaparib 500 mg QD (Part 1)		Rucaparib 240 mg BID (Part 1)		Rucaparib 360 mg BID (Part 1)		Rucaparib 480 mg BID (Part 1)		Rucaparib 600 mg BID (Part 1)		Rucaparib 840 mg BID (Part 1)		Rucaparib 600 mg BID (Part 2A)		Rucaparib 600 mg BID (Part 2B)		Rucaparib 600 mg BID (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		1/3 (33.3%)		3/4 (75%)		4/9 (44.4%)		0/4 (0%)		2/3 (66.7%)		3/8 (37.5%)		4/9 (44.4%)		1/7 (14.3%)		1/3 (33.3%)		19/42 (45.2%)		3/12 (25%)		9/26 (34.6%)
Blood and lymphatic system disorders
Anaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Febrile neutropenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Neutropenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Thrombocytopenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Cardiac disorders
Atrial fibrillation	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Gastrointestinal disorders
Abdominal pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		1/26 (3.8%)
Ascites	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		1/26 (3.8%)
Constipation	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Gastrointestinal haemorrhage	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Haematemesis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Intestinal obstruction	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Large intestinal obstruction	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Nausea	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Obstruction gastric	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pancreatitis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Small intestinal obstruction	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		1/26 (3.8%)
Vomiting	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
General disorders
Generalised oedema	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Non-cardiac chest pain	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pyrexia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Infections and infestations
Cellulitis	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Cytomegalovirus infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Diverticulitis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Epiglottiis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Influenza	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Lower respiratory tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pneumonia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Sepsis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		1/26 (3.8%)
Urinary tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		1/26 (3.8%)
Injury, poisoning and procedural complications
Radius fracture	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Urinary tract stoma complication	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Metabolism and nutrition disorders
Hyponatraemia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell type acute leukaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Malignant neoplasm progression	0/6 (0%)		0/3 (0%)		1/4 (25%)		2/9 (22.2%)		0/4 (0%)		2/3 (66.7%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		1/12 (8.3%)		3/26 (11.5%)
Myodysplastic syndrome	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		2/26 (7.7%)
Nervous system disorders
Cerebrovascular accident	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Headache	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Seizure	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Renal and urinary disorders
Acute kidney injury	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Reproductive system and breast disorders
Vaginal fistula	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Oropharyngeal pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pleural effusion	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pulmonary embolism	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Respiratory failure	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	Rucaparib 40 mg QD (Part 1)		Rucaparib 80 mg QD (Part 1)		Rucaparib 160 mg QD (Part 1)		Rucaparib 300 mg QD (Part 1)		Rucaparib 500 mg QD (Part 1)		Rucaparib 240 mg BID (Part 1)		Rucaparib 360 mg BID (Part 1)		Rucaparib 480 mg BID (Part 1)		Rucaparib 600 mg BID (Part 1)		Rucaparib 840 mg BID (Part 1)		Rucaparib 600 mg BID (Part 2A)		Rucaparib 600 mg BID (Part 2B)		Rucaparib 600 mg BID (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		3/3 (100%)		4/4 (100%)		9/9 (100%)		4/4 (100%)		3/3 (100%)		8/8 (100%)		8/9 (88.9%)		7/7 (100%)		3/3 (100%)		41/42 (97.6%)		12/12 (100%)		26/26 (100%)
Blood and lymphatic system disorders
Anaemia	0/6 (0%)		1/3 (33.3%)		1/4 (25%)		3/9 (33.3%)		1/4 (25%)		0/3 (0%)		4/8 (50%)		3/9 (33.3%)		4/7 (57.1%)		1/3 (33.3%)		30/42 (71.4%)		8/12 (66.7%)		6/26 (23.1%)
Leukopenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		0/26 (0%)
Lymphopenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		2/12 (16.7%)		0/26 (0%)
Neutropenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		1/4 (25%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		2/7 (28.6%)		0/3 (0%)		9/42 (21.4%)		2/12 (16.7%)		3/26 (11.5%)
Thrombocytopenia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		3/7 (42.9%)		0/3 (0%)		8/42 (19%)		4/12 (33.3%)		3/26 (11.5%)
Lymphadenopathy	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Splenomegaly	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Cardiac disorders
Tachycardia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		3/8 (37.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Bradycardia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Palpitations	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Ear and labyrinth disorders
Ear pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		2/12 (16.7%)		0/26 (0%)
Ear congestion	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Eye disorders
Conjunctival hyperaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Vision blurred	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		0/26 (0%)
Macular degeneration	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Mydriasis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Visual acuity reduced	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Visual impairment	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		2/26 (7.7%)
Abdominal distension	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		1/4 (25%)		0/3 (0%)		2/8 (25%)		2/9 (22.2%)		1/7 (14.3%)		0/3 (0%)		11/42 (26.2%)		0/12 (0%)		4/26 (15.4%)
Abdominal pain	1/6 (16.7%)		0/3 (0%)		1/4 (25%)		5/9 (55.6%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		3/9 (33.3%)		1/7 (14.3%)		1/3 (33.3%)		20/42 (47.6%)		5/12 (41.7%)		4/26 (15.4%)
Abdominal pain lower	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		6/42 (14.3%)		2/12 (16.7%)		0/26 (0%)
Abdominal pain upper	1/6 (16.7%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		1/7 (14.3%)		1/3 (33.3%)		5/42 (11.9%)		2/12 (16.7%)		0/26 (0%)
Aphthous ulcer	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		2/12 (16.7%)		0/26 (0%)
Ascites	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		2/9 (22.2%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Constipation	0/6 (0%)		0/3 (0%)		2/4 (50%)		5/9 (55.6%)		0/4 (0%)		0/3 (0%)		3/8 (37.5%)		2/9 (22.2%)		1/7 (14.3%)		0/3 (0%)		22/42 (52.4%)		7/12 (58.3%)		7/26 (26.9%)
Diarrhoea	2/6 (33.3%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		1/3 (33.3%)		1/8 (12.5%)		2/9 (22.2%)		2/7 (28.6%)		3/3 (100%)		17/42 (40.5%)		3/12 (25%)		4/26 (15.4%)
Dry mouth	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		1/4 (25%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		2/26 (7.7%)
Dyspepsia	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		2/12 (16.7%)		6/26 (23.1%)
Flatulence	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		1/12 (8.3%)		0/26 (0%)
Gastrooesophageal reflux disease	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		2/12 (16.7%)		2/26 (7.7%)
Mouth ulceration	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Nausea	3/6 (50%)		1/3 (33.3%)		3/4 (75%)		6/9 (66.7%)		0/4 (0%)		0/3 (0%)		6/8 (75%)		4/9 (44.4%)		4/7 (57.1%)		3/3 (100%)		35/42 (83.3%)		11/12 (91.7%)		11/26 (42.3%)
Stomatitis	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		7/42 (16.7%)		1/12 (8.3%)		0/26 (0%)
Tooth disorder	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Vomiting	2/6 (33.3%)		0/3 (0%)		3/4 (75%)		4/9 (44.4%)		1/4 (25%)		0/3 (0%)		3/8 (37.5%)		5/9 (55.6%)		4/7 (57.1%)		2/3 (66.7%)		24/42 (57.1%)		9/12 (75%)		9/26 (34.6%)
Anal pruritus	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Haemorrhoids	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Intestinal obstruction	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Odynophagia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Oral pain	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Tongue ulceration	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Tooth erosion	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Toothache	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
General disorders
Asthenia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		13/42 (31%)		1/12 (8.3%)		2/26 (7.7%)
Axillary pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Chest pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Chills	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		1/12 (8.3%)		0/26 (0%)
Early satiety	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Fatigue	1/6 (16.7%)		0/3 (0%)		1/4 (25%)		6/9 (66.7%)		2/4 (50%)		1/3 (33.3%)		6/8 (75%)		5/9 (55.6%)		5/7 (71.4%)		1/3 (33.3%)		30/42 (71.4%)		6/12 (50%)		14/26 (53.8%)
Influenza like illness	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		1/12 (8.3%)		0/26 (0%)
Injection site bruising	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Malaise	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Mucosal inflammation	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		2/9 (22.2%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		2/26 (7.7%)
Non-cardiac chest pain	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		1/4 (25%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Oedema peripheral	0/6 (0%)		0/3 (0%)		0/4 (0%)		3/9 (33.3%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		0/12 (0%)		5/26 (19.2%)
Peripheral swelling	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		3/42 (7.1%)		0/12 (0%)		2/26 (7.7%)
Pyrexia	0/6 (0%)		0/3 (0%)		0/4 (0%)		3/9 (33.3%)		0/4 (0%)		1/3 (33.3%)		3/8 (37.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		3/12 (25%)		3/26 (11.5%)
Catheter site inflammation	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Catheter site pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Chest discomfort	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Gait disturbance	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Local swelling	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Nodule	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		1/3 (33.3%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Suprapubic pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Ulcer	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Hepatobiliary disorders
Hepatomegaly	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Portal vein thrombosis	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Immune system disorders
Allergy to arthropod bite	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Anaphylactic reaction	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Hypersensitivity	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Infections and infestations
Ear infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		2/12 (16.7%)		0/26 (0%)
Gastroenteritis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		1/12 (8.3%)		0/26 (0%)
Gingivitis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Herpes simplex	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Lower respiratory tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		1/4 (25%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		1/3 (33.3%)		0/42 (0%)		4/12 (33.3%)		0/26 (0%)
Pneumonia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Tooth infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Upper respiratory tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		12/42 (28.6%)		2/12 (16.7%)		2/26 (7.7%)
Urinary tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		3/7 (42.9%)		0/3 (0%)		8/42 (19%)		3/12 (25%)		5/26 (19.2%)
Viral upper respiratory infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		2/26 (7.7%)
Nasopharyngitis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		5/42 (11.9%)		0/12 (0%)		0/26 (0%)
Conjunctivitis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Furuncle	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Gastroenteritis viral	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Herpes virus infection	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Influenza	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Oral herpes	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Oral infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pharyngitis	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Respiratory tract infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Rhinitis	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		1/26 (3.8%)
Skin candida	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Skin infection	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Staphylococcal infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Urinary tract infection enterococcal	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Wound infection	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		1/4 (25%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Injury, poisoning and procedural complications
Arthropod bite	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Limb injury	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Contusion	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Fall	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		1/26 (3.8%)
Procedural pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Wound	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Investigations
Alanine aminotransferase increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		2/9 (22.2%)		5/7 (71.4%)		1/3 (33.3%)		24/42 (57.1%)		2/12 (16.7%)		6/26 (23.1%)
Aspartate aminotransferase increased	0/6 (0%)		0/3 (0%)		1/4 (25%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		3/9 (33.3%)		5/7 (71.4%)		1/3 (33.3%)		22/42 (52.4%)		2/12 (16.7%)		6/26 (23.1%)
Blood alkaline phosphatase increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		2/9 (22.2%)		4/7 (57.1%)		0/3 (0%)		10/42 (23.8%)		1/12 (8.3%)		0/26 (0%)
Blood bilirubin increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		0/26 (0%)
Blood cholesterol increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		3/9 (33.3%)		1/7 (14.3%)		0/3 (0%)		3/42 (7.1%)		2/12 (16.7%)		3/26 (11.5%)
Blood creatinine increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		1/4 (25%)		1/3 (33.3%)		0/8 (0%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		15/42 (35.7%)		6/12 (50%)		3/26 (11.5%)
Blood potassium increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Blood urea increased	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Gamma-glutamyltransferase increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		1/12 (8.3%)		0/26 (0%)
Lymphocyte count decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Neutrophil count decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		3/9 (33.3%)		1/7 (14.3%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		3/26 (11.5%)
Platelet count decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		3/7 (42.9%)		0/3 (0%)		7/42 (16.7%)		2/12 (16.7%)		2/26 (7.7%)
Transaminases increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		2/26 (7.7%)
Weight decreased	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		8/42 (19%)		1/12 (8.3%)		1/26 (3.8%)
White blood cell count decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		3/9 (33.3%)		1/7 (14.3%)		0/3 (0%)		5/42 (11.9%)		0/12 (0%)		1/26 (3.8%)
Blood magnesium decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Blood phosphorus decreased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Blood urea nitrogen/creatinine ratio increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Breath sounds abnormal	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Heart rate increased	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Neutrophil count increased	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/6 (50%)		0/3 (0%)		0/4 (0%)		6/9 (66.7%)		0/4 (0%)		2/3 (66.7%)		3/8 (37.5%)		1/9 (11.1%)		0/7 (0%)		1/3 (33.3%)		12/42 (28.6%)		3/12 (25%)		10/26 (38.5%)
Dehydration	2/6 (33.3%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		2/7 (28.6%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		2/26 (7.7%)
Hypercalcaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Hypercholesterolaemia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		1/3 (33.3%)		4/42 (9.5%)		1/12 (8.3%)		1/26 (3.8%)
Hyperglycaemia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		2/9 (22.2%)		0/7 (0%)		1/3 (33.3%)		1/42 (2.4%)		1/12 (8.3%)		2/26 (7.7%)
Hyperkalaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Hypertriglyceridaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		2/26 (7.7%)
Hypoalbuminaemia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		1/26 (3.8%)
Hypokalaemia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		1/12 (8.3%)		1/26 (3.8%)
Hypomagnesaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		7/42 (16.7%)		1/12 (8.3%)		0/26 (0%)
Hyponatraemia	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		5/42 (11.9%)		2/12 (16.7%)		0/26 (0%)
Hypophosphataemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		0/26 (0%)
Hyperphosphataemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Hypocalcaemia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		9/42 (21.4%)		3/12 (25%)		3/26 (11.5%)
Back pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		1/4 (25%)		0/3 (0%)		1/8 (12.5%)		2/9 (22.2%)		1/7 (14.3%)		0/3 (0%)		7/42 (16.7%)		2/12 (16.7%)		4/26 (15.4%)
Bone pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Joint swelling	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		3/42 (7.1%)		2/12 (16.7%)		3/26 (11.5%)
Muscle spasms	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		2/42 (4.8%)		1/12 (8.3%)		1/26 (3.8%)
Musculoskeletal chest pain	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Musculoskeletal pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		1/4 (25%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		2/42 (4.8%)		1/12 (8.3%)		1/26 (3.8%)
Musculoskeletal stiffness	1/6 (16.7%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Myalgia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Neck pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Pain in extremity	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		1/12 (8.3%)		2/26 (7.7%)
Bone lesion	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Extremity contracture	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Flank pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		1/26 (3.8%)
Groin pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Joint stiffness	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Muscular weakness	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Musculoskeletal discomfort	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Osteoarthritis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pain in jaw	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Temporomandibular joint syndrome	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	0/6 (0%)		1/3 (33.3%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		1/26 (3.8%)
Cancer pain	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Nervous system disorders
Dizziness	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		2/8 (25%)		2/9 (22.2%)		2/7 (28.6%)		0/3 (0%)		9/42 (21.4%)		1/12 (8.3%)		6/26 (23.1%)
Dysgeusia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		2/8 (25%)		1/9 (11.1%)		1/7 (14.3%)		2/3 (66.7%)		17/42 (40.5%)		2/12 (16.7%)		5/26 (19.2%)
Headache	2/6 (33.3%)		0/3 (0%)		1/4 (25%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		2/7 (28.6%)		1/3 (33.3%)		20/42 (47.6%)		2/12 (16.7%)		2/26 (7.7%)
Lethargy	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		3/12 (25%)		1/26 (3.8%)
Neuropathy peripheral	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		2/3 (66.7%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Paraesthesia	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		1/26 (3.8%)
Restless legs syndrome	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Tremor	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Balance disorder	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Memory impairment	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Peripheral sensory neuropathy	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Seizure	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Sensory loss	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Psychiatric disorders
Agitation	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Anxiety	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		6/42 (14.3%)		0/12 (0%)		2/26 (7.7%)
Depressed mood	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		2/12 (16.7%)		0/26 (0%)
Depression	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		0/12 (0%)		0/26 (0%)
Insomnia	0/6 (0%)		0/3 (0%)		0/4 (0%)		4/9 (44.4%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		6/42 (14.3%)		0/12 (0%)		2/26 (7.7%)
Mental fatigue	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Mental status changes	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Renal and urinary disorders
Dysuria	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		2/8 (25%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		2/26 (7.7%)
Micturition urgency	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Proteinuria	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Urinary incontinence	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		1/12 (8.3%)		1/26 (3.8%)
Pollakiuria	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Hydronephrosis	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Obstructive uropathy	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Renal colic	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Reproductive system and breast disorders
Pelvic pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		5/42 (11.9%)		0/12 (0%)		0/26 (0%)
Vaginal discharge	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Vaginal haemorrhage	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		1/12 (8.3%)		0/26 (0%)
Breast pain	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Pruritus genital	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Vaginal fistula	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Vulvovaginal discomfort	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Vulvovaginal pain	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		1/4 (25%)		1/3 (33.3%)		1/8 (12.5%)		3/9 (33.3%)		2/7 (28.6%)		2/3 (66.7%)		10/42 (23.8%)		2/12 (16.7%)		4/26 (15.4%)
Dysphonia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Dyspnoea	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		3/8 (37.5%)		3/9 (33.3%)		1/7 (14.3%)		1/3 (33.3%)		11/42 (26.2%)		1/12 (8.3%)		4/26 (15.4%)
Dyspnoea exertional	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		3/42 (7.1%)		0/12 (0%)		3/26 (11.5%)
Hypoxia	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Nasal congestion	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Nasal discomfort	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Oropharyngeal pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		1/4 (25%)		0/3 (0%)		1/8 (12.5%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		7/42 (16.7%)		1/12 (8.3%)		1/26 (3.8%)
Pleural effusion	0/6 (0%)		0/3 (0%)		1/4 (25%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		2/42 (4.8%)		0/12 (0%)		0/26 (0%)
Rhinorrhoea	1/6 (16.7%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		1/26 (3.8%)
Catarrh	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Epistaxis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Haemoptysis	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Pleuritic pain	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Wheezing	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		8/42 (19%)		1/12 (8.3%)		1/26 (3.8%)
Blister	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		1/12 (8.3%)		0/26 (0%)
Dry skin	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		1/4 (25%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		6/42 (14.3%)		1/12 (8.3%)		2/26 (7.7%)
Erythema	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		1/12 (8.3%)		0/26 (0%)
Nail discolouration	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		1/26 (3.8%)
Photosensitivity reaction	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		2/9 (22.2%)		1/7 (14.3%)		0/3 (0%)		5/42 (11.9%)		1/12 (8.3%)		1/26 (3.8%)
Pruritus	0/6 (0%)		1/3 (33.3%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		1/7 (14.3%)		0/3 (0%)		6/42 (14.3%)		1/12 (8.3%)		3/26 (11.5%)
Rash	0/6 (0%)		0/3 (0%)		0/4 (0%)		2/9 (22.2%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		8/42 (19%)		1/12 (8.3%)		3/26 (11.5%)
Rash macular	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Rash maculo-papular	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		3/42 (7.1%)		0/12 (0%)		0/26 (0%)
Skin lesion	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Skin ulcer	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		1/12 (8.3%)		0/26 (0%)
Acne	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Hypertrichosis	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Night sweats	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Onychomadesis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Rash papular	0/6 (0%)		0/3 (0%)		0/4 (0%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Skin hypopigmentation	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		1/8 (12.5%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Telangiectasia	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		1/7 (14.3%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)
Vascular disorders
Hot flush	0/6 (0%)		0/3 (0%)		1/4 (25%)		1/9 (11.1%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		2/42 (4.8%)		2/12 (16.7%)		0/26 (0%)
Hypertension	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		4/42 (9.5%)		2/12 (16.7%)		1/26 (3.8%)
Lymphoedema	0/6 (0%)		0/3 (0%)		1/4 (25%)		0/9 (0%)		1/4 (25%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		2/12 (16.7%)		0/26 (0%)
Flushing	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		1/3 (33.3%)		0/42 (0%)		0/12 (0%)		1/26 (3.8%)
Hypotension	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		1/3 (33.3%)		0/8 (0%)		0/9 (0%)		0/7 (0%)		0/3 (0%)		1/42 (2.4%)		0/12 (0%)		0/26 (0%)
Thrombosis	0/6 (0%)		0/3 (0%)		0/4 (0%)		0/9 (0%)		0/4 (0%)		0/3 (0%)		0/8 (0%)		1/9 (11.1%)		0/7 (0%)		0/3 (0%)		0/42 (0%)		0/12 (0%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.