Trial Outcomes & Findings for Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma (NCT NCT00813150)

NCT ID: NCT00813150

Last Updated: 2014-08-15

Results Overview

'Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of \>=25% from lowest level in Serum M-component or (the absolute increase must be \>=0.5 gram per deciliter \[g/dL\]); Urine M component or (the absolute increase must be \>=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase \>10 mg/dL. Bone marrow plasma cell percentage \>=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 96 participants
• Primary outcome timeframe: From the date of randomization until the disease progression or participant's death from any cause whichever occurred first, as assessed up to 72 weeks after end of treatment visit (ie, 46 days after last dose of study medication)
• Results posted on: 2014-08-15

Participant Flow

The study was conducted between 23 December 2008 and 10 January 2013 and recruited patients from 42 study centers in Germany.

A total of 93 participants were randomly allocated and they received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 participants, so, they were excluded from the Intent-to-treat (ITT) analysis data set and so, ITT included 90 participants.

Participant milestones

Measure	Vd (Bortezomib + Dexamethasone) Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Treatment Period STARTED	46	47
Treatment Period Intent-to-treat Participants	43	47
Treatment Period COMPLETED	14	15
Treatment Period NOT COMPLETED	32	32
Long Term Follow-up STARTED	26	31
Long Term Follow-up COMPLETED	2	0
Long Term Follow-up NOT COMPLETED	24	31

Reasons for withdrawal

Measure	Vd (Bortezomib + Dexamethasone) Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Treatment Period Adverse Event	16	15
Treatment Period Death	2	0
Treatment Period Progressive disease	1	0
Treatment Period Complete response	0	1
Treatment Period Stable disease	1	2
Treatment Period Protocol Violation	3	4
Treatment Period Withdrawal by Subject	5	3
Treatment Period Non compliance	0	1
Treatment Period Reason not specified	3	4
Treatment Period Data not available	1	2
Long Term Follow-up Death	0	4
Long Term Follow-up Other	0	3
Long Term Follow-up Lost to Follow-up	2	0
Long Term Follow-up Progression/Relapse	22	24

Baseline Characteristics

Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma

Baseline characteristics by cohort

Measure	Vd (Bortezomib + Dexamethasone) n=43 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.	Total n=90 Participants Total of all reporting groups
Age, Continuous	68 Years STANDARD_DEVIATION 10 • n=5 Participants	71 Years STANDARD_DEVIATION 7 • n=7 Participants	69 Years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	42 Participants n=5 Participants	47 Participants n=7 Participants	89 Participants n=5 Participants
Race/Ethnicity, Customized African	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the disease progression or participant's death from any cause whichever occurred first, as assessed up to 72 weeks after end of treatment visit (ie, 46 days after last dose of study medication)

Population: Intent-to-treat (ITT): Participants who received at least one dose of study medication and in whom the primary efficacy parameter could be assessed at least once under study medication.

'Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of >=25% from lowest level in Serum M-component or (the absolute increase must be >=0.5 gram per deciliter [g/dL]); Urine M component or (the absolute increase must be >=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase >10 mg/dL. Bone marrow plasma cell percentage >=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.

Outcome measures

Measure	Vd (Bortezomib + Dexamethasone) n=43 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Time to Progression of Disease	12.6 Months Interval 9.83 to 14.43	9.9 Months Interval 8.6 to 11.4

SECONDARY outcome

Timeframe: From the date of randomization until the disease progression or participant's death from any cause whichever occured first, as assessed up to 72 weeks after end of treatment visit (ie, 46 days after last dose of study medication)

Population: Intent-to-treat (ITT): all participants who received at least one dose of study medication and in whom the primary efficacy parameter could be assessed at least once under study medication. Participants without progression and who are still alive at the end of the study or dropped out will be censored with the last available date.

PFS is defined as time from randomization to myeloma progression according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of ≥25 percent from lowest response level in Serum M-component and/or (the absolute increase must be ≥0.5 g/dL) Urine M-component and/or (the absolute increase must be ≥200 mg/24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: the absolute percent must be ≥10 percent. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65mmol/L) that can be attributed solely to the plasma cell proliferative disorder. PFS included disease progression as well as death.

Outcome measures

Measure	Vd (Bortezomib + Dexamethasone) n=43 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Progression-Free Survival (PFS)	12.6 Months Interval 9.83 to 14.43	9.9 Months Interval 8.6 to 11.4

SECONDARY outcome

Timeframe: From the date of randomization until Month 49

Population: Intent-to-treat (ITT): Participants received at least 1 dose of study medication were included in the ITT analysis set. Participants still alive at the end of the study or dropped out will be censored with the last available date.

Time interval in months time from randomisation to death from any cause.

Outcome measures

Measure	Vd (Bortezomib + Dexamethasone) n=43 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Overall Survival (OS)	NA Months The values could not be estimated	41.50 Months Interval 24.87 to The upper limit value could not be estimated

SECONDARY outcome

Timeframe: Up to 46 days after last bortezomib dose, or as soon as possible after early discontinuation of study treatment or before start of alternative anti-myeloma therapy

Population: Intent-to-treat (ITT): Participants who received at least one dose of study medication and in whom the primary efficacy parameter could be assessed at least once under study medication.

Percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) is reported in the below table. IMWG criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescencec; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90%; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hour.

Outcome measures

Measure	Vd (Bortezomib + Dexamethasone) n=43 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 Participants Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Overall Response Rate (ORR) - International Myeloma Working Group (IMWG) Response Criteria	74.4 Percentage of participants	70.2 Percentage of participants

Adverse Events

Vd (Bortezomib + Dexamethasone)

Serious events: 15 serious events

Other events: 43 other events

Deaths: 0 deaths

Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide)

Serious events: 14 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vd (Bortezomib + Dexamethasone) n=46 participants at risk Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 participants at risk Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Infections and infestations Pneumonia	8.7% 4/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Diverticulitis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Sepsis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Bronchitis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Cellulitis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Infection	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Varicella	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Constipation	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Abdominal pain	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Diarrhoea	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Diverticulum	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Ileus paralytic	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Inguinal hernia, obstructive	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Vomiting	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Syncope	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Headache	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders IIIrd nerve paresis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Neuropathy peripheral	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Polyneuropathy	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Transient ischaemic attack	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Circulatory collapse	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Haemorrhage	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Hypertension	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Intermittent claudication	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Fatigue	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Multi-organ failure	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Pyrexia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Femoral neck fracture	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Rib fracture	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Osteonecrosis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Pain in extremity	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Anaemia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Disseminated intravascular coagulation	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Bradycardia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Myocardial infarction	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Endocrine disorders Adrenocortical insufficiency acute	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Endocrine disorders Pituitary haemorrhage	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Depression	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Disorientation	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Diplopia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hypercalcaemia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.

Other adverse events

Measure	Vd (Bortezomib + Dexamethasone) n=46 participants at risk Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.	Vcd (Bortezomib + Low-dose Dexamethasone + Cyclophosphamide) n=47 participants at risk Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.
Blood and lymphatic system disorders Thrombocytopenia	37.0% 17/46 • Number of events 87 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	38.3% 18/47 • Number of events 83 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Anaemia	26.1% 12/46 • Number of events 22 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	12.8% 6/47 • Number of events 10 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Leukopenia	8.7% 4/46 • Number of events 10 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	14.9% 7/47 • Number of events 12 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Neutropenia	2.2% 1/46 • Number of events 7 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Diarrhoea	23.9% 11/46 • Number of events 14 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	36.2% 17/47 • Number of events 28 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Constipation	21.7% 10/46 • Number of events 16 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	27.7% 13/47 • Number of events 16 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Nausea	15.2% 7/46 • Number of events 7 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	23.4% 11/47 • Number of events 15 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Vomiting	6.5% 3/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 6 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Abdominal pain	8.7% 4/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Abdominal pain upper	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Stomatitis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Abdominal discomfort	2.2% 1/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Dyspepsia	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Enteritis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Faecal incontinence	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Flatulence	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Mouth ulceration	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Polyneuropathy	15.2% 7/46 • Number of events 14 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	19.1% 9/47 • Number of events 16 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Peripheral sensory neuropathy	6.5% 3/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	19.1% 9/47 • Number of events 13 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Dizziness	15.2% 7/46 • Number of events 8 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Headache	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 11 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Paraesthesia	8.7% 4/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Dysgeusia	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Neuropathy peripheral	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Neuralgia	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Sciatica	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Ageusia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Hypoaesthesia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Burning sensation	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Hemicephalgia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Hypogeusia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Hyposmia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Neurotoxicity	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Post herpetic neuralgia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Nervous system disorders Tremor	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Fatigue	28.3% 13/46 • Number of events 15 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	38.3% 18/47 • Number of events 32 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Oedema peripheral	15.2% 7/46 • Number of events 7 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	21.3% 10/47 • Number of events 13 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Pyrexia	6.5% 3/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	14.9% 7/47 • Number of events 10 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Pain	8.7% 4/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Asthenia	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Oedema	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Chills	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Feeling cold	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Local swelling	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Chest pain	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Discomfort	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Gait Disturbance	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
General disorders Mucosal inflammation	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Nasopharyngitis	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	23.4% 11/47 • Number of events 11 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Herpes zoster	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 7 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Bronchitis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	12.8% 6/47 • Number of events 6 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Respiratory tract infection	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Cystitis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Urinary tract infection	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Eye infection	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Oesophageal candidiasis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Oral candidiasis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Oral herpes	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Rhinitis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Sinusitis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Upper respiratory tract infection	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Acute tonsillitis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Diverticulitis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Fungal infection	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Gastroenteritis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Hordeolum	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Infection	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Infective aneurysm	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Influenza	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Orchitis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Paronychia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Pneumonia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Pulmonary mycosis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Infections and infestations Pyelonephritis acute	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Back pain	6.5% 3/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	14.9% 7/47 • Number of events 7 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Bone pain	8.7% 4/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Pain in extremity	8.7% 4/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 2/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Muscle spasms	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Exostosis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Muscle twitching	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Sensation of heaviness	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Musculoskeletal and connective tissue disorders Spinal disorder	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Haemoglobin decreased	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Weight decreased	8.7% 4/46 • Number of events 6 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations C-reactive protein increased	6.5% 3/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Blood alkaline phosphatase increased	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Blood lactate dehydrogenase increased	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Weight increased	4.3% 2/46 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Blood creatinine increased	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Platelet count decreased	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Alanine aminotransferase increased	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Blood creatine phosphokinase increased	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Eastern cooperative oncology group performance status worse	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Heart rate increased	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Protein urine present	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Investigations Transaminases increased	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hyperglycaemia	4.3% 2/46 • Number of events 11 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Anorexia	10.9% 5/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hypercalcaemia	2.2% 1/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hypocalcaemia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hypokalaemia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Gout	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Hypertension	10.9% 5/46 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Hypotension	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Haematoma	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Orthostatic hypotension	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Deep vein thrombosis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Circulatory collapse	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Flushing	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Peripheral arterial occlusive disease	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Thrombophlebitis supeficial	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Thrombosis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Vascular disorders Venous thrombosis limb	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Cough	10.9% 5/46 • Number of events 6 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Lung infiltration	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Sleep disorder	8.7% 4/46 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Insomnia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	10.6% 5/47 • Number of events 5 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Depression	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Restlessness	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Agitation	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Dyssomnia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Psychiatric disorders Mood altered	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Rash	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Alopecia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Dry skin	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Pruritus	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Rash pruritic	2.2% 1/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Rash vesicular	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Conjunctivitis	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Visual impairment	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	8.5% 4/47 • Number of events 4 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Lacrimation increased	2.2% 1/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	4.3% 2/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Colour blindness acquired	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Eye disorders Keratitis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Ear and labyrinth disorders Vertigo	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	19.1% 9/47 • Number of events 9 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Ear and labyrinth disorders Hypoacusis	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Post procedural haemorrhage	2.2% 1/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Traumatic haematoma	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Arthropod bite	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Drug dispensing error	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Excoriation	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Eyelid injury	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Fall	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Laceration	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Tachycardia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Arrhythmia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Bradycardia	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Cardiac disorder	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Cardiac failure	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Right ventricular hypertrophy	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Supraventricular extrasystoles	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Cardiac disorders Ventricular extrasystoles	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Nocturia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Strangury	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Haematuria	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Leukocyturia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Nephrolithiasis	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Renal and urinary disorders Urinary incontinence	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	4.3% 2/46 • Number of events 2 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	6.4% 3/47 • Number of events 3 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders Dry mouth	0.00% 0/46 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	2.1% 1/47 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.
Gastrointestinal disorders dysphagia	2.2% 1/46 • Number of events 1 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.	0.00% 0/47 • Approximately 5 years A total of 96 patients were randomly allocated to the 2 treatment arms in the study. 93 patients received at least 1 dose of study drug and were included in the safety analysis. Of these follow-up data on treatment response was not available for 3 patients, so, they were excluded from the Intent-to-treat analysis data set.

Additional Information

Therapeutic Areas Director

Jan-Cil Germany

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60