Trial Outcomes & Findings for A Dose-finding Study of Dalotuzumab in Subjects With Advanced Solid Tumors (MK-0646-002) (NCT NCT00635778)

Last Updated: 2018-10-09

Results Overview

Blood samples were obtained for analysis of steady-state serum concentration of dalotuzumab at 336 hours (C336) after the first maintenance dose of dalotuzumab. The C336 of dalotuzumab after intravenous administration is presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

50 participants

Primary outcome timeframe

2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)

Results posted on

2018-10-09

Participant Flow

This study enrolled participants with metastatic or locally advanced solid tumors, associated with insulin-like growth factor receptor type 1 (IGF-1R) protein expression, that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. Other inclusion/exclusion criteria applied.

Participant milestones

Participant milestones
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by intravenous (IV) infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Overall Study STARTED	1	3	3	8	8	21	6
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	1	3	3	8	8	21	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by intravenous (IV) infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Overall Study Adverse Event	1	0	0	3	3	6	1
Overall Study Withdrawal by Subject	0	0	0	1	0	1	1
Overall Study Progressive disease	0	3	3	4	5	14	4

Baseline Characteristics

All enrolled participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Total n=50 Participants Total of all reporting groups
Age, Continuous	62.0 Years STANDARD_DEVIATION NA • n=5 Participants	74.3 Years STANDARD_DEVIATION 9.9 • n=7 Participants	60.3 Years STANDARD_DEVIATION 8.6 • n=5 Participants	71.3 Years STANDARD_DEVIATION 6.5 • n=4 Participants	59.1 Years STANDARD_DEVIATION 7.6 • n=21 Participants	58.1 Years STANDARD_DEVIATION 11.8 • n=10 Participants	53.7 Years STANDARD_DEVIATION 21.2 • n=115 Participants	61.0 Years STANDARD_DEVIATION 12.7 • n=6 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	10 Participants n=10 Participants	2 Participants n=115 Participants	17 Participants n=6 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants	7 Participants n=21 Participants	11 Participants n=10 Participants	4 Participants n=115 Participants	33 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=4 Participants • All enrolled participants.	0 Participants n=21 Participants • All enrolled participants.	0 Participants n=10 Participants • All enrolled participants.	0 Participants n=115 Participants • All enrolled participants.	0 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) Asian	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	1 Participants n=5 Participants • All enrolled participants.	1 Participants n=4 Participants • All enrolled participants.	1 Participants n=21 Participants • All enrolled participants.	1 Participants n=10 Participants • All enrolled participants.	0 Participants n=115 Participants • All enrolled participants.	4 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=4 Participants • All enrolled participants.	0 Participants n=21 Participants • All enrolled participants.	0 Participants n=10 Participants • All enrolled participants.	0 Participants n=115 Participants • All enrolled participants.	0 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=4 Participants • All enrolled participants.	0 Participants n=21 Participants • All enrolled participants.	1 Participants n=10 Participants • All enrolled participants.	0 Participants n=115 Participants • All enrolled participants.	1 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) White	1 Participants n=5 Participants • All enrolled participants.	3 Participants n=7 Participants • All enrolled participants.	2 Participants n=5 Participants • All enrolled participants.	6 Participants n=4 Participants • All enrolled participants.	4 Participants n=21 Participants • All enrolled participants.	17 Participants n=10 Participants • All enrolled participants.	5 Participants n=115 Participants • All enrolled participants.	38 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=4 Participants • All enrolled participants.	0 Participants n=21 Participants • All enrolled participants.	0 Participants n=10 Participants • All enrolled participants.	0 Participants n=115 Participants • All enrolled participants.	0 Participants n=6 Participants • All enrolled participants.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • All enrolled participants.	0 Participants n=7 Participants • All enrolled participants.	0 Participants n=5 Participants • All enrolled participants.	1 Participants n=4 Participants • All enrolled participants.	3 Participants n=21 Participants • All enrolled participants.	2 Participants n=10 Participants • All enrolled participants.	1 Participants n=115 Participants • All enrolled participants.	7 Participants n=6 Participants • All enrolled participants.
Number of Prior Chemotherapy Regimens	3.0 Regimens STANDARD_DEVIATION NA • n=5 Participants	2.7 Regimens STANDARD_DEVIATION 0.6 • n=7 Participants	3.0 Regimens STANDARD_DEVIATION 0.0 • n=5 Participants	3.0 Regimens STANDARD_DEVIATION 0.0 • n=4 Participants	3.0 Regimens STANDARD_DEVIATION 0.0 • n=21 Participants	2.9 Regimens STANDARD_DEVIATION 0.3 • n=10 Participants	2.5 Regimens STANDARD_DEVIATION 0.8 • n=115 Participants	2.9 Regimens STANDARD_DEVIATION 0.4 • n=6 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 0	0 Participants n=5 Participants • All enrolled participants	1 Participants n=7 Participants • All enrolled participants	1 Participants n=5 Participants • All enrolled participants	1 Participants n=4 Participants • All enrolled participants	3 Participants n=21 Participants • All enrolled participants	10 Participants n=10 Participants • All enrolled participants	4 Participants n=115 Participants • All enrolled participants	20 Participants n=6 Participants • All enrolled participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 1	0 Participants n=5 Participants • All enrolled participants	2 Participants n=7 Participants • All enrolled participants	2 Participants n=5 Participants • All enrolled participants	6 Participants n=4 Participants • All enrolled participants	5 Participants n=21 Participants • All enrolled participants	10 Participants n=10 Participants • All enrolled participants	1 Participants n=115 Participants • All enrolled participants	26 Participants n=6 Participants • All enrolled participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS = 2	1 Participants n=5 Participants • All enrolled participants	0 Participants n=7 Participants • All enrolled participants	0 Participants n=5 Participants • All enrolled participants	1 Participants n=4 Participants • All enrolled participants	0 Participants n=21 Participants • All enrolled participants	1 Participants n=10 Participants • All enrolled participants	1 Participants n=115 Participants • All enrolled participants	4 Participants n=6 Participants • All enrolled participants

PRIMARY outcome

Timeframe: 2 weeks post first maintenance dose of study drug (3 weeks post loading dose of study drug)

Population: All participants who received dalotuzumab and had blood samples drawn for pharmacokinetic (PK) analyses.

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=2 Participants Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=19 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=5 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Steady-state Serum Concentration of Dalotuzumab at 336 Hours (C336) After the First Maintenance Dose	4.78 μg/mL Standard Deviation NA Not calculated on only 1 participant	7.48 μg/mL Standard Deviation 8.50	54.57 μg/mL Standard Deviation 24.64	33.00 μg/mL Standard Deviation 24.90	25.95 μg/mL Standard Deviation 26.22	24.39 μg/mL Standard Deviation 27.63	86.73 μg/mL Standard Deviation 44.56

PRIMARY outcome

Timeframe: The entire treatment period (Up to 18 months)

Population: All participants who received at least one dose of study drug.

Dose-limiting toxicities (DLT) were assessed and graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE). A DLT was defined as the occurrence of any of the following events, that were judged by the study investigator, to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5 degrees Celsius; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity (except alopecia and inadequately treated diarrhea, nausea, and vomiting, and hyperglycemia lasting less than 5 days; and Grade 3 or greater hyperglycemia lasting for more than 5 days in spite of optimal medical management.

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Number of Participants Who Experience One or More Dose- Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 18 months post first dose of study drug

Population: All participants who received at least one dose of study therapy.

Complete Response (disappearance of all target lesions) or Partial Response (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) using Response Criteria in Solid Tumors (RECIST). Tumor response was assessed prior to first dose and every 8 weeks beginning pre-dose of Week 9 for up to 18 months. The best response out of all measurements for each participant was used for determining CR and PR.

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Number of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 1

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 1.

IGF-1R expression was measured in pre- and post-dose biopsy samples using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) assays. Results were expressed as a percent change from baseline in IG1-FR expression for participants pooled across all dose arms in the study and calculated by study week. A post-dose decrease in IGF-1R expression was an indication of target engagement by dalotuzumab. A larger percent change correlated with a greater target engagement.

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=41 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Level at Week 1	118.56 Percent change Interval -61.54 to 377.08	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Prior to second and subsequent doses of study drug (Up to 1 year post-first dose)

Population: All participants who received one dose of study therapy.

The formation of HAHAs may block efficacy by prematurely clearing dalotuzumab and limit the possibility of future dalotuzumab therapy. Blood samples for the measurement of serum levels of HAHAs were obtained prior to treatment with dalotuzumab, and pre-dose Week 3, Week 5, pre-dose every 8 subsequent weeks, and end of treatment (post-study: 4 weeks after last dose of study drug). Positive HAHA status for a participant is defined as testing positive on both the screening and immunodepletion assays at one or more visits.

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 Participants Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Number of Participants With a Positive Human-anti-humanized-antibody (HAHA) Titer	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 5

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 5

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=25 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 5	150.94 Percent change Interval -49.35 to 421.84	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 9

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 9

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=6 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 9	150.69 Percent change Interval 55.0 to 246.51	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 13

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=4 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 13	138.11 Percent change Interval 128.42 to 164.29	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 17

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 17

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 17	140.72 Percent change Interval 120.0 to 198.05	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 21

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 21	150.00 Percent change Interval 102.4 to 161.05	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 25

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 25

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=3 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 25	157.49 Percent change Interval 114.74 to 170.78	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 29

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 29

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=2 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 29	174.95 Percent change Interval 172.63 to 177.27	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 33

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 33

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 33	158.95 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 37

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 37

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 37	186.32 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 41

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 41

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 41	173.68 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 45

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 45

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 45	140.00 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 49

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 49

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 49	137.89 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 53

Population: All participants who took at least one dose of study drug and had available IGF-1R protein data for Baseline and Week 53

Outcome measures

Outcome measures
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 Participants Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Percent Change From Baseline in Serum IGF-1R Protein Level at Week 53	198.99 Percent change Not calculated on only 1 participant	—	—	—	—	—	—

Adverse Events

Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg

Serious events: 5 serious events

Other events: 8 other events

Deaths: 1 deaths

Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg

Serious events: 6 serious events

Other events: 8 other events

Deaths: 1 deaths

Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg

Serious events: 9 serious events

Other events: 21 other events

Deaths: 1 deaths

Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 participants at risk Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 participants at risk Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 participants at risk Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 participants at risk Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Haematemesis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Obstruction gastric	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Infusion related reaction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Abdominal abscess	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Cellulitis	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Osteomyelitis acute	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Sepsis	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Device failure	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Encephalopathy	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Lethargy	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Mental status changes	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Bladder pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Ureteric obstruction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Alveolitis allergic	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Dalotuzumab 2.5 mg/kg / Dalotuzumab 2.5 mg/kg n=1 participants at risk Participants received a loading dose of dalotuzumab 2.5 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 2.5 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 5.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 participants at risk Participants received a loading dose of dalotuzumab 5.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 10.0 mg/kg / Dalotuzumab 5.0 mg/kg n=3 participants at risk Participants received a loading dose of dalotuzumab 10.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 20.0 mg/kg / Dalotuzumab 5.0 mg/kg n=8 participants at risk Participants received a loading dose of dalotuzumab 20.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 5.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 10.0 mg/kg n=21 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 10.0 mg/kg administered by IV infusion every two weeks for up to 18 months.	Dalotuzumab 15.0 mg/kg / Dalotuzumab 15.0 mg/kg n=6 participants at risk Participants received a loading dose of dalotuzumab 15.0 mg/kg administered by IV infusion. Two weeks following completion of the loading dose, participants received a maintenance dose of dalotuzumab 15.0 mg/kg administered by IV infusion every two weeks for up to 18 months.
Gastrointestinal disorders Ascites	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	28.6% 6/21 • Number of events 6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Bradycardia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Cardiac disorders Palpitations	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Ear and labyrinth disorders Deafness	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Eye disorders Dry eye	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Eye disorders Myodesopsia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 5 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	37.5% 3/8 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Epigastric discomfort	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Flatulence	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Melaena	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	47.6% 10/21 • Number of events 10 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Proctalgia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 7/21 • Number of events 10 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Chills	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Fatigue	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	50.0% 4/8 • Number of events 7 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	37.5% 3/8 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	57.1% 12/21 • Number of events 12 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 4/6 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Hernia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Infusion related reaction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Oedema	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Oedema peripheral	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Pyrexia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
General disorders Suprapubic pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Hepatobiliary disorders Portal vein occlusion	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Body tinea	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Candidiasis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Ear infection	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Fungal oesophagitis	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Osteomyelitis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Otitis externa	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Sinusitis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Skin infection	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 5 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 5 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood albumin decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	37.5% 3/8 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood creatinine increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood glucose increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood lactate dehydrogenase increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood magnesium decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood magnesium increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Blood uric acid increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Glomerular filtration rate decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Haemoglobin urine present	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations International normalised ratio increased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Platelet count decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Prothrombin time prolonged	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	66.7% 2/3 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	37.5% 3/8 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	50.0% 4/8 • Number of events 5 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Investigations White blood cell count decreased	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Acidosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Anorexia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	28.6% 6/21 • Number of events 6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 4 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperammonaemia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercreatininaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	19.0% 4/21 • Number of events 6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	100.0% 1/1 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	14.3% 3/21 • Number of events 3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Coccydynia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Ageusia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Asterixis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Ataxia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Balance disorder	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Memory impairment	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Paraesthesia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Somnolence	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Nervous system disorders Tremor	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Agitation	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Depression	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Polyuria	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Ureteric stenosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Urinary incontinence	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Renal and urinary disorders Urinary retention	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Reproductive system and breast disorders Breast pain	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Reproductive system and breast disorders Penile pain	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Reproductive system and breast disorders Scrotal oedema	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	9.5% 2/21 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	23.8% 5/21 • Number of events 5 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	25.0% 2/8 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung infiltration	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary cavitation	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash follicular	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	12.5% 1/8 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Vascular disorders Hypotension	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 1/3 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	4.8% 1/21 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	33.3% 2/6 • Number of events 2 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.
Vascular disorders Lymphorrhoea	100.0% 1/1 • Number of events 1 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/3 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/8 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/21 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.	0.00% 0/6 • Up to 19 months (up to 18 months of treatment with study drug plus 1 month of follow-up) The safety population consisted of all participants who received at least one dose of study drug.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER