Trial Outcomes & Findings for Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone (NCT NCT00507416)

Last Updated: 2014-05-01

Results Overview

PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria. Progressive disease requires 1 of the following: * Increase of ≥ 25% from nadir in: * Serum M-component (absolute increase ≥ 0.5 g/dl) * Urine M-component (absolute increase ≥ 200 mg/24 hours) * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 100 mg/dl) * Bone marrow plasma cell percentage (absolute % ≥ 10%) * Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. * Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

502 participants

Primary outcome timeframe

From randomization until disease progression. Median follow-up time was 43 months.

Results posted on

2014-05-01

Participant Flow

Participants took part in the study at 158 investigative sites in the United States from 26 June 2007 to 28 March 2013

Participants with previously untreated multiple myeloma were randomized in a 1:1:1 ratio to one of three treatment groups: VD: Velcade (bortezomib) and dexamethasone; VTD: Velcade, thalidomide, and dexamethasone; VMP: Velcade, melphalan, and prednisone.

Participant milestones

Participant milestones
Measure	Bortezomib and Dexamethasone Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Overall Study STARTED	168	167	167
Overall Study Treated (Safety Population)	165	158	163
Overall Study Completed 8 Treatment Cycles	82	60	69
Overall Study COMPLETED	50	42	53
Overall Study NOT COMPLETED	118	125	114

Reasons for withdrawal

Reasons for withdrawal
Measure	Bortezomib and Dexamethasone Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Overall Study Adverse Event	58	67	65
Overall Study Protocol Violation	1	2	0
Overall Study Lack ofEfficacy / Physician Decision	7	7	8
Overall Study Progressive Disease	20	10	13
Overall Study Patient declined further treatment	18	14	11
Overall Study Other	11	16	13
Overall Study Did not Receive Study Treatment	3	9	4

Baseline Characteristics

Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib and Dexamethasone n=168 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Total n=502 Participants Total of all reporting groups
Age, Continuous	72.6 years STANDARD_DEVIATION 9.35 • n=5 Participants	71.3 years STANDARD_DEVIATION 8.73 • n=7 Participants	71.3 years STANDARD_DEVIATION 8.67 • n=5 Participants	71.7 years STANDARD_DEVIATION 8.92 • n=4 Participants
Age, Customized ≥ 65 years	140 participants n=5 Participants	135 participants n=7 Participants	139 participants n=5 Participants	414 participants n=4 Participants
Age, Customized ≥ 75 years	84 participants n=5 Participants	64 participants n=7 Participants	62 participants n=5 Participants	210 participants n=4 Participants
Age, Customized ≥ 80 years	40 participants n=5 Participants	27 participants n=7 Participants	23 participants n=5 Participants	90 participants n=4 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	97 Participants n=7 Participants	77 Participants n=5 Participants	241 Participants n=4 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	70 Participants n=7 Participants	90 Participants n=5 Participants	261 Participants n=4 Participants
Race/Ethnicity, Customized White	131 participants n=5 Participants	124 participants n=7 Participants	118 participants n=5 Participants	373 participants n=4 Participants
Race/Ethnicity, Customized Black	23 participants n=5 Participants	31 participants n=7 Participants	29 participants n=5 Participants	83 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Other	10 participants n=5 Participants	10 participants n=7 Participants	15 participants n=5 Participants	35 participants n=4 Participants
Race/Ethnicity, Customized Not Reported	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment United States	168 participants n=5 Participants	167 participants n=7 Participants	167 participants n=5 Participants	502 participants n=4 Participants

PRIMARY outcome

Timeframe: From randomization until disease progression. Median follow-up time was 43 months.

Population: Intent-to-treat (all randomized participants)

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=168 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Progression Free Survival (PFS)	14.7 months Interval 12.0 to 18.6	15.4 months Interval 12.6 to 24.2	17.3 months Interval 14.8 to 20.3

SECONDARY outcome

Timeframe: Response assessed every other cycle for up to 13 cycles (49 weeks).

Population: Response-Evaluable population, defined as all participants who received at least 1 dose of any study drug, have measurable disease at baseline, and have at least one post-baseline M-protein measurement.

Overall response defined as a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR), assessed by the Investigator using the IMWG uniform response criteria. CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours (h). PR requires 1 of the following: * ≥50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to \<200 mg/24 h, or * If M-protein not measurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels, or * If FLC not measurable, a ≥ 50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%. If present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=147 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=133 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=145 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Percentage of Participants With an Overall Response	73 percentage of participants	80 percentage of participants	70 percentage of participants

SECONDARY outcome

Timeframe: Response assessed every other cycle, for up to 13 cycles (49 weeks).

Participants with a best overall response of complete response, defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. Response was assessed by the Investigator using the IMWG uniform response criteria.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=147 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=133 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=145 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Percentage of Participants With a Complete Response	3 percentage of participants	4 percentage of participants	4 percentage of participants

SECONDARY outcome

Timeframe: Response assessed every other cycle for up to 13 cycles (49 weeks).

Complete response is defined by negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. Very good partial response is defined by 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 \<100 mg per 24 hours. Response was assessed by the Investigator using the IMWG uniform response criteria.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=147 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=133 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=145 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Percentage of Participants With a Complete Response or a Very Good Partial Response	37 percentage of participants	51 percentage of participants	41 percentage of participants

SECONDARY outcome

Timeframe: From first documented response until disease progression. Median follow-up time was 43 months.

Population: Participants with an overall response

Duration of response is defined in participants with an overall response as the time between first documentation of response and disease progression. Responders without disease progression were censored at the last clinical assessment of response.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=107 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=106 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=101 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Duration of Response	18.3 months Interval 14.3 to 24.2	22.4 months Interval 12.7 to 29.1	19.8 months Interval 16.4 to 23.3

SECONDARY outcome

Timeframe: From randomization until death. Median follow-up time was 43 months.

Population: Intent to treat

Overall survival is defined as the time between randomization and death. Participants still alive at the cutoff date or lost to follow-up were censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=168 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Overall Survival	49.8 months Interval 35.7 to Upper limit was not estimable due to low number of events	51.5 months Interval 38.5 to Upper limit was not estimable due to low number of events	53.1 months Interval 41.1 to Upper limit was not estimable due to low number of events

SECONDARY outcome

Timeframe: From randomization until alternative therapy. Median follow-up time was 43 months.

Population: Intent to Treat

Time to alternative therapy is defined as the time between randomization and alternative therapy. Participants who did not receive alternative therapy were censored at the time of last contact.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=168 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Time to Alternative Therapy	19.7 months Interval 16.0 to 27.8	24.5 months Interval 16.6 to 27.6	19.0 months Interval 15.2 to 23.1

SECONDARY outcome

Timeframe: Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13

Population: Intent-to-treat population with available data at each time point (indicated by "n").

The European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement.

Outcome measures

Outcome measures
Measure	Bortezomib and Dexamethasone n=168 Participants Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=167 Participants Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 3, Day 1 (n=129, 115, 125)	1.3 units on a scale Standard Deviation 25.40	-4.4 units on a scale Standard Deviation 27.04	2.0 units on a scale Standard Deviation 30.82
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 13, Day 1 (n=67, 52, 61)	-10.2 units on a scale Standard Deviation 36.00	-8.5 units on a scale Standard Deviation 32.87	1.0 units on a scale Standard Deviation 35.16
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 5, Day 1 (n=114, 98, 107)	-4.9 units on a scale Standard Deviation 30.36	-6.1 units on a scale Standard Deviation 27.47	-0.4 units on a scale Standard Deviation 29.24
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 7, Day 1 (n=89, 79, 84)	-3.3 units on a scale Standard Deviation 32.58	-8.6 units on a scale Standard Deviation 31.86	-4.7 units on a scale Standard Deviation 28.61
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 9, Day 1 (n=87, 66, 67)	-4.2 units on a scale Standard Deviation 33.55	-8.1 units on a scale Standard Deviation 28.16	-1.0 units on a scale Standard Deviation 28.55
Change From Baseline in EORTC QLQ-C30 - Global Health Status Cycle 11, Day 1 (n=71, 61, 65)	-11.6 units on a scale Standard Deviation 33.67	-7.9 units on a scale Standard Deviation 29.54	2.8 units on a scale Standard Deviation 31.72

Adverse Events

Bortezomib and Dexamethasone

Serious events: 88 serious events

Other events: 57 other events

Deaths: 0 deaths

Bortezomib, Thalidomide, and Dexamethasone

Serious events: 92 serious events

Other events: 68 other events

Deaths: 0 deaths

Bortezomib, Melphalan and Prednisone

Serious events: 83 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Millennium Pharmaceuticals Inc

Phone: 1-800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Bortezomib and Dexamethasone n=165 participants at risk Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=158 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=163 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Infections and infestations Pneumonia	10.9% 18/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	7.6% 12/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	6.1% 10/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Lobar pneumonia	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Bronchitis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Sepsis	1.8% 3/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Bacteraemia	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Septic shock	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Bacterial sepsis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Device related sepsis	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Urosepsis	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Urinary tract infection	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Pyelonephritis acute	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Gastroenteritis	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Diverticulitis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Appendicitis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Peritonitis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Cellulitis	1.8% 3/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Periorbital cellulitis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Peritonitis bacterial	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Pneumonia bacterial	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Herpes zoster	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Herpes zoster disseminated	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Clostridium difficile colitis	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Staphylococcal abscess	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Staphylococcal bacteraemia	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Bursitis infective	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Oesophageal candidiasis	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Escherichia urinary tract infection	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Fungal skin infection	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Device related infection	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Pneumonia pneumococcal	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Infections and infestations Viral infection	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Diarrhoea	7.3% 12/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	3.2% 5/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	4.9% 8/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Vomiting	1.8% 3/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	3.2% 5/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	3.7% 6/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Nausea	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Constipation	3.6% 6/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.9% 3/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Abdominal pain	2.4% 4/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.9% 3/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Ileus	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Intestinal obstruction	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Gastrointestinal disorders Pancreatitis acute	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.

Other adverse events
Measure	Bortezomib and Dexamethasone n=165 participants at risk Participants received bortezomib (Velcade) 1.3 mg/m\^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Thalidomide, and Dexamethasone n=158 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Bortezomib, Melphalan and Prednisone n=163 participants at risk Participants received bortezomib 1.3 mg/m\^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m\^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m\^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/\^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Investigations Weight decreased	2.4% 4/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	3.7% 6/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Platelet count decreased	1.8% 3/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	4.3% 7/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood sodium decreased	1.8% 3/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.9% 3/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood uric acid increased	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.9% 3/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Neutrophil count decreased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	3.7% 6/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood alkaline phosphatase increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood urea increased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Protein total increased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Weight increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.9% 3/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood bilirubin increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Troponin T increased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood calcium increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood chloride decreased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood creatinine decreased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood glucose increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood immunoglobulin G increased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood phosphorus decreased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Blood potassium increased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Breath sounds abnormal	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Carbon monoxide diffusing capacity decreased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Lymphocyte count decreased	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Lymphocyte count increased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Investigations Red blood cell count decreased	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Dysgeusia	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	2.5% 4/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Post herpetic neuralgia	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Tremor	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Balance disorder	1.2% 2/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Paraesthesia	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.8% 3/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Headache	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.2% 2/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Somnolence	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Ageusia	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Cranial nerve disorder	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Dysarthria	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	1.3% 2/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Memory impairment	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Ataxia	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.61% 1/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Hemiparesis	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Hypogeusia	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Polyneuropathy	0.00% 0/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.63% 1/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.
Nervous system disorders Presyncope	0.61% 1/165 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/158 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.	0.00% 0/163 • Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks. Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.