Trial Outcomes & Findings for Safety and Efficacy Clinical Study of SNS-595 in Patients With Platinum-Resistant Ovarian Cancer (NCT NCT00408603)

Last Updated: 2017-07-27

Results Overview

Response rate was calculated per investigator's tumor assessment based on GOG-RECIST, which includes radiographic imaging, physical examination results, and CA-125 levels. No independent review of CT scans (lesion assessments) was performed. CR: disappearance of all target and nontarget lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at baseline, is required for ovarian carcinoma studies. PR is \>= 30% decrease in the sum of LD of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

183 participants

Primary outcome timeframe

GOG-RECIST assessment obtained on cycle2, 4 and 6 Day 21for patients treated with 48 mg/m2 SNS-595 and Day 28 for patients treated with 60 mg/m2, through 28 (±14) days afte the last treatment at the end of safety follow up period

Results posted on

2017-07-27

Participant Flow

Participant milestones

Participant milestones
Measure	Stage 48 mg/m2 All Stage 1 patients will receive voreloxin injection Voreloxin Injection: All Stage 1 patients in initial dose level receive voreloxin injection at 48 mg/m2 administered once every 21 days up to 6 cycles.	Stage 60 mg/m2 Following safety of 48 mg/m2 group, next Stagel is 60mg/m2 at 28 day periods up to 6 cycles.	Stage 75 mg/m2 Following safety of 60 mg/m2 group, next Stage is 75 mg/m2 at 28 day periods up to 6 cycles.
Overall Study STARTED	69	39	75
Overall Study COMPLETED	65	37	35
Overall Study NOT COMPLETED	4	2	40

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Clinical Study of SNS-595 in Patients With Platinum-Resistant Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	48 mg/m2 n=65 Participants 48 mg/m2 every 21 days	60 mg/m2 n=37 Participants 60 mg/m2 every 28 days	75 mg/m2 n=35 Participants 75 mg/m2 every 28 days	Total n=137 Participants Total of all reporting groups
Age, Continuous	60 years STANDARD_DEVIATION 9.87 • n=93 Participants	62.7 years STANDARD_DEVIATION 10.51 • n=4 Participants	57.6 years STANDARD_DEVIATION 12.13 • n=27 Participants	60.1 years STANDARD_DEVIATION 10.74 • n=483 Participants
Sex: Female, Male Female	65 Participants n=93 Participants	37 Participants n=4 Participants	35 Participants n=27 Participants	137 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=93 Participants	37 Participants n=4 Participants	35 Participants n=27 Participants	137 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized Asian	5 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	8 Participants n=483 Participants
Race/Ethnicity, Customized Black or African	4 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Race/Ethnicity, Customized White or Caucasian	56 Participants n=93 Participants	35 Participants n=4 Participants	31 Participants n=27 Participants	122 Participants n=483 Participants
Race/Ethnicity, Customized Other, Philippines	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Height (cm)	162.4 cm STANDARD_DEVIATION 6.75 • n=93 Participants	161.9 cm STANDARD_DEVIATION 7.01 • n=4 Participants	163.9 cm STANDARD_DEVIATION 7.01 • n=27 Participants	162.7 cm STANDARD_DEVIATION 6.88 • n=483 Participants
Weight (kg)	75.1 kg STANDARD_DEVIATION 17.21 • n=93 Participants	71.2 kg STANDARD_DEVIATION 20.52 • n=4 Participants	69.9 kg STANDARD_DEVIATION 15.39 • n=27 Participants	72.7 kg STANDARD_DEVIATION 17.76 • n=483 Participants
BSA (m2)	1.8 m2 STANDARD_DEVIATION 0.2 • n=93 Participants	1.7 m2 STANDARD_DEVIATION 0.24 • n=4 Participants	1.8 m2 STANDARD_DEVIATION 0.2 • n=27 Participants	1.8 m2 STANDARD_DEVIATION 0.21 • n=483 Participants

PRIMARY outcome

Timeframe: GOG-RECIST assessment obtained on cycle2, 4 and 6 Day 21for patients treated with 48 mg/m2 SNS-595 and Day 28 for patients treated with 60 mg/m2, through 28 (±14) days afte the last treatment at the end of safety follow up period

Population: Safety Population which included all patients who received any amount of vosaroxin

Outcome measures

Outcome measures
Measure	48 mg/m2 n=65 Participants 48 mg/m2 every 21 days	60 mg/m2 n=37 Participants 60 mg/m2 every 28 days	75 mg/m2 n=35 Participants 75 mg/m2 every 28 days	Total n=137 Participants Overall
Overall Response Rate (CR+PR) Per Investigator Assessment Based on GOG-RECIST Criteria	7 Participants	4 Participants	3 Participants	14 Participants

SECONDARY outcome

Timeframe: From the first teratment of Vosaroxin to the end of Cycle 6 or 28 days after the last treatment at the end of safety follow up period if continued in the extended treatment period

Population: Safety population which included all patients who received any amount of vosaroxin

PFS is the the time between the date the patient first received Vosaroxin and the earliest date of disease progression. For patients who experienced disease progression, the date of disease progression will be the earliest date on which disease progression is indicated based on the rules. For patients who died with no indication of disease progression, the date of death will be the earliest date on which death is documented based on the rules. For patients who have no indication of disease progression or death, the censoring date will be the Date of Confirmed Contact from the last Survival Follow-Up CRF, or if not in survival follow-up, then the Assessment Date from the last GOG-RECIST CRF, or if no response assessment available, Date of Last Visit / Contact from Extended Treatment Completion CRF if in extended treatment, or from Cycle 6 Completion / Early Termination CRF if not in extended treatment.

Outcome measures

Outcome measures
Measure	48 mg/m2 n=65 Participants 48 mg/m2 every 21 days	60 mg/m2 n=37 Participants 60 mg/m2 every 28 days	75 mg/m2 n=35 Participants 75 mg/m2 every 28 days	Total n=137 Participants Overall
Progression-free Survival (PFS) Using Kaplan-Meier Methods	83 Days Interval 49.0 to 90.0	61 Days Interval 53.0 to 134.0	103 Days Interval 53.0 to 167.0	81 Days Interval 57.0 to 93.0

Adverse Events

48 mg/m2

Serious events: 15 serious events

Other events: 63 other events

Deaths: 7 deaths

60 mg/m2

Serious events: 9 serious events

Other events: 37 other events

Deaths: 2 deaths

75 mg/m2

Serious events: 14 serious events

Other events: 35 other events

Deaths: 3 deaths

Total

Serious events: 38 serious events

Other events: 135 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Linda Neuman, Vice President, Clinical Development

Sunesis Pharmaceuticals, Inc.

Phone: (650) 266-3760

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	48 mg/m2 n=65 participants at risk 48 mg/m2 every 21 days	60 mg/m2 n=37 participants at risk 60 mg/m2 every 28 days	75 mg/m2 n=35 participants at risk 75 mg/m2 every 28 days	Total n=137 participants at risk Overall
Blood and lymphatic system disorders Anaemia	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	3.6% 5/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Febrile neutropenia	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	28.6% 10/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	10.9% 15/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Leukopenia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Neutropenia	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Nausea	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Small intestinal obstruction	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Vomiting	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
General disorders Fatigue	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
General disorders Pyrexia	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Abdominal abscess	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Abdominal wall infection	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Bacillus infection	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Bacteraemia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Bacterial infection	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Catheter bacteraemia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Cellulitis	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Cystitis	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Diverticulitis	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Gastroenteritis	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Neutropenic sepsis	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Urinary tract infection bacterial	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Infections and infestations Wound infection	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Metabolism and nutrition disorders Failure to thrive	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Nervous system disorders Brain stem syndrome	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Renal and urinary disorders Nephropathy	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Renal and urinary disorders Renal disorder	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Vascular disorders Deep vein thrombosis	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.

Other adverse events
Measure	48 mg/m2 n=65 participants at risk 48 mg/m2 every 21 days	60 mg/m2 n=37 participants at risk 60 mg/m2 every 28 days	75 mg/m2 n=35 participants at risk 75 mg/m2 every 28 days	Total n=137 participants at risk Overall
Metabolism and nutrition disorders Hypomagnesaemia	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	13.5% 5/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	8.6% 3/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	8.0% 11/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Metabolism and nutrition disorders Vitamin B12 deficiency	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 4/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	16.2% 6/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	8.6% 3/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	9.5% 13/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Back pain	16.9% 11/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	21.6% 8/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	20.0% 7/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	19.0% 26/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Bone pain	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Musculoskeletal and connective tissue disorders Flank pain	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Anaemia	21.5% 14/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	37.8% 14/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	37.1% 13/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	29.9% 41/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Febrile neutropenia	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	8.1% 3/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.1% 7/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Leukopenia	6.2% 4/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.8% 8/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Lymph node pain	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Lymphadenopathy	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Neutropenia	32.3% 21/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	21.6% 8/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	51.4% 18/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	34.3% 47/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	11.4% 4/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Atrial fibrillation	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Mitral valve incompetence	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Palpitations	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Pericardial effusion	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Sinus tachycardia	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Tachycardia	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	3.6% 5/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Ear and labyrinth disorders Ear pain	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Ear and labyrinth disorders Vertigo	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 4/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Blepharospasm	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Dark circles under eyes	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Dry eye	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Lacrimation increased	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Ocular hyperaemia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Photophobia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.9% 1/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Photopsia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Vision blurred	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.7% 1/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.7% 2/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	4.4% 6/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Eye disorders Visual disturbance	1.5% 1/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.73% 1/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Abdominal discomfort	4.6% 3/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	2.2% 3/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Abdominal distension	24.6% 16/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	24.3% 9/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	25.7% 9/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	24.8% 34/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Abdominal hernia	0.00% 0/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	5.4% 2/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Abdominal mass	3.1% 2/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	0.00% 0/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	1.5% 2/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.
Gastrointestinal disorders Abdominal pain	33.8% 22/65 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	18.9% 7/37 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	34.3% 12/35 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.	29.9% 41/137 • Approximately 50% of patients were assessed for AEs for 112 days or less and the other approximate 50% were assessed for 112 to 700 days.