Trial Outcomes & Findings for Pazopanib Paediatric Phase II Trial Children's Oncology Group (COG) in Solid Tumors (NCT NCT01956669)

NCT ID: NCT01956669

Last Updated: 2020-08-12

Results Overview

ORR was defined as the percentage of participants achieving either a Complete Response (CR) or partial Response (PR) based on the Investigator review. The responses were assessed by CT or MRI based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST1.1). CR, disappearance of all target and non-target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion. Confirmation was based on the disease assessment at 1 cycle or at the next scheduled visit after the initial response. Only descriptive analysis performed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

From date of first dose of study treatment up to 55 months

Results posted on

2020-08-12

Participant Flow

This study was conducted at 30 centers in 7 countries: Canada (2), Czech Republic (1), France (1), Hungary (1), Slovakia (1), Spain (1) and USA (23).

154 patients were planned to be enrolled in the study. A total of 57 patients were randomized and analyzed: cohort 1 (12), cohort 2 (11), cohort 3 (10), cohort 4 (10), cohort 5 (4), cohort 6 (4) and cohort 7 (6).

Participant milestones

Participant milestones
Measure	Cohort 1: Rhabdomyosarcoma (RMS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 4 (Osteosarcoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Study STARTED	12	11	10	10	4	4	6
Overall Study PK Set	11	11	10	10	4	4	6
Overall Study PKES Set	4	0	3	0	1	1	5
Overall Study Biomarker Set	12	11	9	9	3	4	3
Overall Study Per Protocol Set (PP Set)	9	10	6	9	4	4	5
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	12	11	10	10	4	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Rhabdomyosarcoma (RMS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 4 (Osteosarcoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Study Disease Progression	12	7	7	8	4	3	5
Overall Study Adverse Event	0	2	2	1	0	0	0
Overall Study Physician Decision	0	2	0	0	0	1	0
Overall Study Withdrawal by Subject	0	0	1	1	0	0	1

Baseline Characteristics

Pazopanib Paediatric Phase II Trial Children's Oncology Group (COG) in Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 4 (Osteosarcoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Total n=57 Participants Total of all reporting groups
Age, Continuous	9.8 Years STANDARD_DEVIATION 3.82 • n=5 Participants	15.7 Years STANDARD_DEVIATION 1.19 • n=7 Participants	12.6 Years STANDARD_DEVIATION 4.67 • n=5 Participants	14.1 Years STANDARD_DEVIATION 3.57 • n=4 Participants	9.8 Years STANDARD_DEVIATION 5.91 • n=21 Participants	13.0 Years STANDARD_DEVIATION 4.24 • n=8 Participants	5.3 Years STANDARD_DEVIATION 4.80 • n=8 Participants	11.9 Years STANDARD_DEVIATION 4.84 • n=24 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	5 Participants n=8 Participants	24 Participants n=24 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	33 Participants n=24 Participants
Race/Ethnicity, Customized White/Caucasian/European heritage	9 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=8 Participants	1 Participants n=8 Participants	36 Participants n=24 Participants
Race/Ethnicity, Customized African American/African heritage	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	10 Participants n=24 Participants
Race/Ethnicity, Customized White Arabic/White North African heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants
Race/Ethnicity, Customized American Indian/Alaskan native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Central/South Asian heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Japanese heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Southeast Asian heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Native Hawaiian/other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Missing	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	4 Participants n=24 Participants

PRIMARY outcome

Timeframe: From date of first dose of study treatment up to 55 months

Population: mITT Set

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Percentage of Participants Achieving Objective Response Rate (ORR) in Subjects' With Tumors of Primary Interest (RMS, NRSTS or Ewing Sarcoma/pPNET)	8.3 Percentage of Participants Interval 0.4 to 33.9	0.0 Percentage of Participants Interval 0.0 to 23.8	0.0 Percentage of Participants Interval 0.0 to 25.9	—	—	—	—

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 55 months

Population: mITT set

ORR was defined as the percentage of participants achieving either a Complete Response (CR) or partial Response (PR) based on the Investigator review. For solid tumors with measurable diseases, such as osteosarcoma, the responses was based on RECIST1.1. CR, disappearance of all target and non target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion. For neuroblastoma with bone marrow response, morphology was determined by hematoxylin and eosin staining of the marrow and aspirates. For neuroblastoma MIBG+ only, the responses was assessed using Curie scale for lesion scoring; For hepatoblastoma, assessment may have included the serum AFP response, in addition to the RECIST1.1 methodology. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Percentage of Participants Achieving Objective Response Rate (ORR) in Subjects' With Tumors of Secondary Interest (Osteosarcoma, mNeuroblastoma, eNeuroblastoma or Hepatoblastoma)	0.0 Percentage of Participants Interval 0.0 to 25.9	0.0 Percentage of Participants Interval 0.0 to 52.7	0.0 Percentage of Participants Interval 0.0 to 52.7	0.0 Percentage of Participants Interval 0.0 to 39.3	—	—	—

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 59 months

Population: mITT set

PFS was defined as the interval between the date of first dose of study medication and the earliest date of disease progression or death due to any cause. Disease progression was based on radiographic evidence, and assessments made by the investigator. According to RECIST1.1, disease progression was defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. For participants who did not progress or die, PFS was censored at the date of last adequate assessment or date of last adequate assessment prior to initiation of new anti-cancer therapy. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Progression Free Survival (PFS) as Assessed by the Investigator by Cohort	1.8 Months Interval 1.0 to 1.8	1.8 Months Interval 0.3 to 13.8	2.3 Months Interval 0.2 to 13.5	1.9 Months Interval 0.5 to 5.3	4.9 Months Interval 0.8 to 6.4	5.4 Months Interval 3.6 to 24.4	1.8 Months Interval 0.5 to 1.9

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 59 months

Population: mITT set

The TTP was defined as the interval between the date of first dose of protocol therapy and the earliest date of disease progression or death due to disease under study. Subjects were considered to have progressive disease if they had documented progression based on radiologic assessment as determined by investigator review. According to RECIST1.1, disease progression was defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Time to Progression (TTP) by Cohort	1.8 Months Interval 1.0 to 1.8	1.8 Months Interval 0.3 to 13.8	2.3 Months Interval 0.2 to 13.5	1.9 Months Interval 0.5 to 5.3	4.9 Months Interval 0.8 to 6.4	14.9 Months Interval 5.4 to 24.4	1.8 Months Interval 0.5 to 1.9

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 55 months

Population: mITT set

CBR was defined as the percentage of participants achieving either a confirmed complete response (CR) or confirmed partial response (PR) or Stable Disease (SD) for at least two protocol scheduled disease assessments based on RECIST1.1. CR, disappearance of all target and non-target lesions; PR, at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study enrollment, also no new lesion or progression of any non-target measurable lesion; SD, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Percentage of Participants Achieving Clinical Benefit Rate (CBR) by Cohort	8.3 Percentage of Participants Interval 0.4 to 33.9	27.3 Percentage of Participants Interval 7.9 to 56.4	20.0 Percentage of Participants Interval 3.7 to 50.7	20.0 Percentage of Participants Interval 3.7 to 50.7	50.0 Percentage of Participants Interval 9.8 to 90.2	25.0 Percentage of Participants Interval 1.3 to 75.1	0.0 Percentage of Participants Interval 0.0 to 39.3

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 59 months

Population: mITT Set

DoR was defined as the time from initial response to the first documented disease progression or death due to any cause, and was determined only for those participants from the mITT population with a confirmed response (CR or PR). Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Duration of Response (DOR) by Cohort	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events	NA Months NA: Not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 61 months

Population: mITT Set

OS was defined as the time from the first dose of the study medication until death due to any cause. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=10 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Overall Survival (OS) by Cohort	5.6 Months Interval 2.2 to 14.2	14.6 Months Interval 1.5 to 20.1	NA Months Interval 4.3 to NA: Not estimable due to insufficient number of participants with events	5.5 Months Interval 1.5 to 7.0	NA Months Interval 2.6 to NA: Not estimable due to insufficient number of participants with events	5.4 Months Interval 3.6 to 24.4	5.7 Months Interval 0.6 to NA: Not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)

Population: PKES set

AUC0-8h and AUClast were calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=5 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Area Under the Plasma Concentration-time Curve Calculated From Time 0 to 8 h Postdose (AUC0-8h) and Calculated to the Last Quantifiable Concentration Point (AUClast) of Pazopanib by Cohort AUC0-8h (C1D1)	195 ng*hr/mL Geometric Coefficient of Variation 19.0	214 ng*hr/mL Geometric Coefficient of Variation 93.2	—	—	135 ng*hr/mL Geometric Coefficient of Variation 60.2	—	—
Area Under the Plasma Concentration-time Curve Calculated From Time 0 to 8 h Postdose (AUC0-8h) and Calculated to the Last Quantifiable Concentration Point (AUClast) of Pazopanib by Cohort AUC0-8h (C1D15)	388 ng*hr/mL Geometric Coefficient of Variation 55.9	266 ng*hr/mL Geometric Coefficient of Variation 36.1	475 ng*hr/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	566 ng*hr/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	229 ng*hr/mL Geometric Coefficient of Variation 89.5	—	—
Area Under the Plasma Concentration-time Curve Calculated From Time 0 to 8 h Postdose (AUC0-8h) and Calculated to the Last Quantifiable Concentration Point (AUClast) of Pazopanib by Cohort AUClast (C1D1)	194 ng*hr/mL Geometric Coefficient of Variation 19.6	189 ng*hr/mL Geometric Coefficient of Variation 65.8	—	—	135 ng*hr/mL Geometric Coefficient of Variation 60.2	—	—
Area Under the Plasma Concentration-time Curve Calculated From Time 0 to 8 h Postdose (AUC0-8h) and Calculated to the Last Quantifiable Concentration Point (AUClast) of Pazopanib by Cohort AUClast (C1D15)	966 ng*hr/mL Geometric Coefficient of Variation 58.1	633 ng*hr/mL Geometric Coefficient of Variation 35.4	1230 ng*hr/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	1490 ng*hr/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	607 ng*hr/mL Geometric Coefficient of Variation 85.0	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)

Population: PKES set

Cmax was calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=5 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Observed Maximum Plasma Concentration (Cmax) of Pazopanib by Cohort Cmax (C1D1)	34.7 ng/mL Geometric Coefficient of Variation 14.7	35.6 ng/mL Geometric Coefficient of Variation 75.9	0.0 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—	22.4 ng/mL Geometric Coefficient of Variation 73.7	—	—
Observed Maximum Plasma Concentration (Cmax) of Pazopanib by Cohort Cmax (C1D15)	56.7 ng/mL Geometric Coefficient of Variation 53.3	42.0 ng/mL Geometric Coefficient of Variation 42.3	69.6 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	80.2 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	33.4 ng/mL Geometric Coefficient of Variation 95.9	—	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose); Cycle 1 Day 15 ± 1 day (0, 0.5, 1, 2, 4, 6 and 8 hours post-dose)

Population: PKES set

Tmax was calculated using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) and the LLOQ was 0.100 µg/mL. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=5 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Time to Reach Peak or Maximum Concentration (Tmax) of Pazopanib by Cohort Tmax (C1D15)	2.50 Hours Interval 2.0 to 3.03	1.00 Hours Interval 1.0 to 1.0	3.47 Hours Interval 3.47 to 3.47	3.03 Hours Interval 3.03 to 3.03	3.00 Hours Interval 0.98 to 4.0	—	—
Time to Reach Peak or Maximum Concentration (Tmax) of Pazopanib by Cohort Tmax (C1D1)	1 Hours Interval 0.0 to 2.0	2.02 Hours Interval 1.0 to 5.97	0.00 Hours Interval 0.0 to 0.0	—	2.00 Hours Interval 0.0 to 6.0	—	—

SECONDARY outcome

Timeframe: From date of first dose of study treatment up to 61 months

Population: PK set. Only participants with a drug-related grade 2 and above hypertension event included in the analysis

The relationship between toxicity (including hypertension) and pharmacokinetic parameters (pazopanib trough concentration) was analyzed. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=2 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=2 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Pazopanib Steady-state Trough (Ctrough) Levels for Participants With Drug-related Grade 2 and Above Hypertension	—	97.1 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	35.7 ng/mL Geometric Coefficient of Variation 22.6	35.7 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	38.0 ng/mL Geometric Coefficient of Variation 20.8	63.7 ng/mL Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—

SECONDARY outcome

Timeframe: predose Cycle 1 Day 1, Cycle 2 Day 1

Population: Biomarker set. Only participants with single nucleotide variant (SNV) were included in the analysis. The FLT1 gene was found to have a single SNV in one evaluable neuroblastoma participant.

The frequency of genetic alterations observed in participants was presented by high and low baseline plasma levels for Vascular endothelial growth factor A (VEGF-A) and Vascular endothelial growth factor receptor 1 (VEGFR-1) biomarkers. The VEGFA and VEGFR1 levels above the median were classified as high and participants with median levels or below were classified as low. Only descriptive analysis performed for participants presenting with a genetic alteration.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=1 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · FLT1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · PLCG1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · VHL	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · FLT1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · KDR	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · HIF1A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · KRAS	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · PIK3R1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · MAPK1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA Low · PLCG1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · VHL	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · FLT1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · KDR	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · HIF1A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · KRAS	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · PIK3R1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · MAPK1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFA High · PLCG1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · VHL	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · KDR	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · HIF1A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · KRAS	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · PIK3R1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · MAPK1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 Low · PLCG1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · VHL	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · FLT1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · KDR	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · HIF1A	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · KRAS	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · PIK3R1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Genetic Alterations by Low and High Values of VEGFA and VEGFR1 VEGFR1 High · MAPK1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: predose Cycle 1 Day 1, Cycle 2 Day 1

Population: Biomarker set

The following biomarker parameters were analyzed: proto-oncogene c-KIT (c-KIT), Fibroblast growth factor (FGF), Placental growth factor PGF), Angiopoietin-1 receptor (TIE2), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Vascular endothelial growth factor receptor 1 (VEGFR-1) and Vascular endothelial growth factor receptor 2 (VEGFR-2)). Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=9 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=9 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort PGF (C1D1)	19.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 245.7	8.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 27.6	9.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 36.9	10.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 37.0	9.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 6.2	13.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 126.6	8.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 29.7
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort PGF (C2D1)	54.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 259.4	27.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 74.9	37.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 82.9	63.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 113.8	30.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 300.5	225.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 840.1	39.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort TIE2 (C1D1)	8086.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 26.5	8180.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 25.0	7280.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 15.6	8574.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 7.7	7439.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 4.6	8179.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 30.0	7842.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 18.3
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort TIE2 (C2D1)	8340.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 11.5	7788.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 11.5	7650.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 22.7	7894.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 17.4	8026.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 28.2	6824.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 32.0	8540.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-A (C1D1)	63.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 133.8	46.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 66.1	74.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 98.0	82.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 62.0	48.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 39.0	62.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 268.3	129.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 46.6
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-A (C2D1)	123.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 140.6	77.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 166.8	171.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 126.0	179.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 98.7	219.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 40.4	1057.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 750.0	208.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-D (C1D1)	354.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 54.6	372.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 20.5	394.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 21.6	375.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 43.9	645.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 108.7	351.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 12.1	370.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 75.9
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-D (C2D1)	434.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 77.4	501.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 43.0	448.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 16.9	551.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 14.4	501.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 50.1	791.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 51.1	400.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGFR-1 (C1D1)	394.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 292.3	175.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 174.4	224.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 121.7	134.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 113.7	95.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 42.9	367.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 130.8	173.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 109.6
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGFR-2 (C1D1)	31451.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 22.6	31745.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 20.6	33724.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 15.8	34993.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 17.6	31682.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 12.1	39342.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 14.7	30780.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 6.0
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGFR-2 (C2D1)	25099.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 22.9	23059.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 21.6	23502.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 1.0	22154.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 15.1	25385.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 42.9	13621.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 68.5	26266.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort c-KIT (C2D1)	110154.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 14.1	99962.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 8.2	94307.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 15.1	99989.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 18.9	121497.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 23.0	71216.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 2.0	154558.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort FGF (C2D1)	15.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 68.9	6.2 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	5.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—	6.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—	—
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-C (C1D1)	121.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 1.6	152.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 84.7	—	—	—	—	—
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGF-C (C2D1)	105.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	339.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—	—	—	—	—
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort VEGFR-1 (C2D1)	87.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 98.5	534.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 709.9	93.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 121.1	140.0 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 231.3	69.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 4.9	76.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 14.6	1811.6 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort c-KIT (C1D1)	139522.4 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 29.4	142526.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 24.3	135024.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 25.9	137317.7 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 23.9	142630.1 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 18.0	113596.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 26.6	119921.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 30.6
Summary for Plasma Biomarkers Levels on Cycle 1 Day 1 and Cycle 2 Day 1 by Cohort FGF (C1D1)	7.8 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 63.1	6.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 71.1	8.3 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 59.1	5.9 picogram/milliliter (pg/mL) Geometric Coefficient of Variation 6.0	—	13.5 picogram/milliliter (pg/mL) Geometric Coefficient of Variation NA NA: Not estimable due to insufficient number of participants with events	—

SECONDARY outcome

Timeframe: predose Cycle 1 Day 1, Cycle 2 Day 1

Population: Biomarker set. Only patient with steady state trough plasma Pazopanib concentration included in the analysis.

Participants with steady state trough concentration median levels for the following biomarker parameters (proto-oncogene c-KIT (c-KIT), Fibroblast growth factor (FGF), Placental growth factor PGF), Angiopoietin-1 receptor (TIE2), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Vascular endothelial growth factor receptor 1 (VEGFR-1) and Vascular endothelial growth factor receptor 2 (VEGFR-2)) above the median levels were classified as high or below median levels were classified as low. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Non-rhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=9 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=9 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=3 Participants Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort PGF high trough concentration	—	—	78.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	15.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	45.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort c-KIT high trough concentration	—	—	-76081.1 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-40512.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-51199.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort c-KIT low trough concentration	-13480.5 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-44973.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-48764.1 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-35678.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort TIE2 low trough concentration	1212.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-1514.9 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-918.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-473.0 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGF-A high trough concentration	—	—	358.8 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	34.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-73.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGF-A low trough concentration	2436.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	18.5 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	52.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	39.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGF-D high trough concentration	—	—	88.0 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	139.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	187.5 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort FGF high trough concentration	—	—	-7.0 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	—	—	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort PGF low trough concentration	—	5.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	28.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	—	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort TIE2 high trough concentration	—	—	2553.0 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-509.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-2708.2 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGF-D low trough concentration	423.2 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	44.1 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	153.5 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	90.8 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGFR-1 high trough concentration	—	—	-217.5 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	955.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-49.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGFR-1 low trough concentration	484.1 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-67.2 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-7.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-741.3 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGFR-2 high trough concentration	—	—	-2620.0 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-16136.9 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-16838.7 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—
Summary for Change From Baseline Levels of Plasma Biomarkers by High and Low Pazopanib Steady State Trough Concentration and Cohort VEGFR-2 low trough concentration	-12130.8 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	-7795.4 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-8588.1 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—	-10529.6 picogram/milliliter (pg/mL) Standard Deviation NA NA: Not estimable due to insufficient number of participants with events	—

Adverse Events

Cohort 1: Rhabdomyosarcoma (RMS)

Serious events: 2 serious events

Other events: 12 other events

Deaths: 3 deaths

Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS)

Serious events: 5 serious events

Other events: 11 other events

Deaths: 0 deaths

Cohort 3: Ewing Sarcoma/pPNET (Ewing)

Serious events: 3 serious events

Other events: 10 other events

Deaths: 1 deaths

Cohort 4 (Osteosarcoma)

Serious events: 3 serious events

Other events: 10 other events

Deaths: 3 deaths

Cohort 5: Measurable Neuroblastoma (mNeuroblastoma)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 6: Evaluable Neuroblastoma (eNeuroblastma)

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

Cohort 7 (Hepatoblastoma)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

All Subjects

Serious events: 17 serious events

Other events: 57 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 4 (Osteosarcoma) n=10 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	All Subjects n=57 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Cardiopulmonary failure	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Left ventricular dysfunction	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Pain	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Cellulitis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Sepsis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Skin infection	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Wound infection	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood creatinine increased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Gamma-glutamyltransferase increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Hepatic enzyme increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Intracranial pressure increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Pleural effusion	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).

Other adverse events

Other adverse events
Measure	Cohort 1: Rhabdomyosarcoma (RMS) n=12 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 2: Nonrhabdomyosarcomatous Soft Tissue Sarcoma (NRSTS) n=11 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 3: Ewing Sarcoma/pPNET (Ewing) n=10 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 4 (Osteosarcoma) n=10 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 5: Measurable Neuroblastoma (mNeuroblastoma) n=4 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 6: Evaluable Neuroblastoma (eNeuroblastma) n=4 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	Cohort 7 (Hepatoblastoma) n=6 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.	All Subjects n=57 participants at risk Subjects were treated with pazopanib GW786034 tablets at a dose of 450 mg/m\^2/dose or as a powder in suspension at a dose of 225 mg/m\^2/dose. The maximum daily dose administered was to be 800 mg for the tablet and 400 mg for suspension. If 225 mg/m\^2/dose was not tolerated (\>=2 DLTs in 6 evaluable subjects), the dose for subjects who required suspension was reduced to 160 mg/m\^2/dose. A cycle was defined as 28 days with no rest periods between cycles.
Blood and lymphatic system disorders Leukopenia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Blood and lymphatic system disorders Anaemia	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	21.1% 12/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Blood and lymphatic system disorders Lymphopenia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Blood and lymphatic system disorders Neutropenia	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Sinus bradycardia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Sinus tachycardia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Supraventricular extrasystoles	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Cardiac disorders Tachycardia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Ear and labyrinth disorders Cerumen impaction	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Ear and labyrinth disorders Deafness bilateral	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Ear and labyrinth disorders Vertigo	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Endocrine disorders Hypothyroidism	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	19.3% 11/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Conjunctival haemorrhage	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Erythema of eyelid	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Eye pain	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Eye pruritus	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Eyelash discolouration	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Eye disorders Vision blurred	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Abdominal distension	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Abdominal pain	41.7% 5/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	36.4% 4/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 19/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Cheilitis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Constipation	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	14.0% 8/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Diarrhoea	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	27.3% 3/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	29.8% 17/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Dyspepsia	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Flatulence	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Frequent bowel movements	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Haematochezia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Nausea	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 5/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 3/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	35.1% 20/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Oral dysaesthesia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Oral pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Toothache	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Gastrointestinal disorders Vomiting	66.7% 8/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	66.7% 4/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	35.1% 20/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Asthenia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Fatigue	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	27.3% 3/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	29.8% 17/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Feeling jittery	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Gait disturbance	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Influenza like illness	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Nodule	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Non-cardiac chest pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	27.3% 3/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Oedema peripheral	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Peripheral swelling	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
General disorders Pyrexia	41.7% 5/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	66.7% 4/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	28.1% 16/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Hepatobiliary disorders Hepatic steatosis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Folliculitis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Nasopharyngitis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Otitis media acute	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Pharyngitis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Rhinitis	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Sinusitis	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Upper respiratory tract infection	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Infections and infestations Urinary tract infection	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	8.8% 5/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Fall	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Gastrostomy tube site complication	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Tongue injury	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Wound	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood alkaline phosphatase increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Injury, poisoning and procedural complications Wound complication	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Activated partial thromboplastin time prolonged	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Alanine aminotransferase increased	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 3/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	24.6% 14/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Amylase increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Aspartate aminotransferase increased	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	66.7% 4/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	28.1% 16/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood alkaline phosphatase	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood bilirubin increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood creatinine increased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood thyroid stimulating hormone increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	27.3% 3/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Blood urea increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Carbon dioxide decreased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Cardiac murmur	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Creatinine urine increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Ejection fraction decreased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Electrocardiogram QT prolonged	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Gamma-glutamyltransferase increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 3/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Haemoglobin increased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations International normalised ratio increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Lipase increased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Lymphocyte count decreased	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	8.8% 5/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Lymphocyte count increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Monocyte count increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Neutrophil count decreased	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	17.5% 10/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Platelet count decreased	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 5/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	28.1% 16/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Protein total increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Red blood cell count decreased	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Urine analysis abnormal	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Vanillyl mandelic acid urine increased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations Weight decreased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	12.3% 7/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Investigations White blood cell count decreased	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 5/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 3/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	22.8% 13/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Decreased appetite	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	36.4% 4/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 3/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	38.6% 22/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypercalcaemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hyperkalaemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hyperphosphataemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypoalbuminaemia	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	12.3% 7/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypocalcaemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypokalaemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Metabolism and nutrition disorders Vitamin D deficiency	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Back pain	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	36.4% 4/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 5/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	50.0% 2/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	28.1% 16/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	8.8% 5/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Osteopenia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	24.6% 14/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Musculoskeletal and connective tissue disorders Trismus	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Cognitive disorder	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Dizziness	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Dysgeusia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Headache	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	27.3% 3/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	19.3% 11/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Hypersomnia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Lethargy	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Paraesthesia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Nervous system disorders Somnolence	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Psychiatric disorders Anxiety	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Psychiatric disorders Depression	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Psychiatric disorders Insomnia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Psychiatric disorders Intentional self-injury	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Psychiatric disorders Irritability	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Bladder pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Chromaturia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Dysuria	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Haematuria	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	12.3% 7/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Haemoglobinuria	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Leukocyturia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Micturition urgency	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Pollakiuria	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Renal and urinary disorders Proteinuria	33.3% 4/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	22.8% 13/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Reproductive system and breast disorders Amenorrhoea	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Reproductive system and breast disorders Genital pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Reproductive system and breast disorders Pelvic pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Reproductive system and breast disorders Vulvovaginal pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Catarrh	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Cough	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	22.8% 13/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.5% 6/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	12.3% 7/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Hiccups	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Hypoxia	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 2/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	7.0% 4/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	25.0% 3/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	14.0% 8/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	8.8% 5/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Acne	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Dermatitis exfoliative generalised	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Hair colour changes	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	30.0% 3/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	75.0% 3/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	22.8% 13/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Macule	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Skin depigmentation	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Skin erosion	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	5.3% 3/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	9.1% 1/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Skin and subcutaneous tissue disorders Urticaria	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Vascular disorders Flushing	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Vascular disorders Hot flush	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	1.8% 1/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Vascular disorders Hypertension	8.3% 1/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	18.2% 2/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	20.0% 2/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	40.0% 4/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	25.0% 1/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	33.3% 2/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	22.8% 13/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).
Vascular disorders Hypotension	0.00% 0/12 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/11 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	10.0% 1/10 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	0.00% 0/4 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	16.7% 1/6 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).	3.5% 2/57 • Adverse Events were collected from first dose of study treatment plus 30 days post treatment, up to a maximum duration of 889 days. Any sign and symptom that occurs during the study treatment plus the 30 days post-treatment. Maximum exposure to study treatments = 889 days (cohort 1), 405 days (cohort 2), 404 days (cohort 3), 191 days (cohort 4), 196 days (cohort 5), 194 days (cohort 6) and 54 days (cohort 7).

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER