Trial Outcomes & Findings for Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (NCT NCT01023308)

NCT ID: NCT01023308

Last Updated: 2020-03-17

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

767 participants

Primary outcome timeframe

45 months

Results posted on

2020-03-17

Participant Flow

Participant milestones

Participant milestones
Measure	Panobinostat + Bortezomib Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Study STARTED	387	381
Overall Study COMPLETED	102	102
Overall Study NOT COMPLETED	285	279

Reasons for withdrawal

Reasons for withdrawal
Measure	Panobinostat + Bortezomib Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Study Abnormal test proceedure results	3	8
Overall Study Administrative problems	2	1
Overall Study Adverse Event	130	66
Overall Study Death	21	17
Overall Study Disease progression	82	153
Overall Study New Cancer therapy	4	7
Overall Study Protocol Violation	3	4
Overall Study Untreated	5	5
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	34	18

Baseline Characteristics

Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.	Total n=768 Participants Total of all reporting groups
Age, Continuous	62.4 years STANDARD_DEVIATION 9.34 • n=5 Participants	61.8 years STANDARD_DEVIATION 9.43 • n=7 Participants	62.1 years STANDARD_DEVIATION 9.38 • n=5 Participants
Sex: Female, Male Female	185 Participants n=5 Participants	176 Participants n=7 Participants	361 Participants n=5 Participants
Sex: Female, Male Male	202 Participants n=5 Participants	205 Participants n=7 Participants	407 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	249 Participants n=5 Participants	250 Participants n=7 Participants	499 Participants n=5 Participants
Race/Ethnicity, Customized Asian	128 Participants n=5 Participants	104 Participants n=7 Participants	232 Participants n=5 Participants
Race/Ethnicity, Customized Black	5 Participants n=5 Participants	17 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: 45 months

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	207 number of events	260 number of events

PRIMARY outcome

Timeframe: 45 months

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	11.99 months Interval 10.32 to 12.94	8.80 months Interval 7.56 to 9.23

SECONDARY outcome

Timeframe: 45 months

Number of OS events

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone	134 Number of OS events	152 Number of OS events

SECONDARY outcome

Timeframe: 45 months

Population: FAS

survival time in months

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone	40.28 months Interval 35.02 to 44.81	35.78 months Interval 28.98 to 40.64

SECONDARY outcome

Timeframe: 45 months

Best overall response based on mEBMT criteria per investigator assessment

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	60.7 % participants with response	54.6 % participants with response

SECONDARY outcome

Timeframe: 45 months

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Time to Response Per Investigator Assessment (mEBMT Criteria) of Response Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	1.51 time to response in months Interval 1.41 to 1.64	2.00 time to response in months Interval 1.61 to 2.79

SECONDARY outcome

Timeframe: 45 months

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	13.14 duration of response in months Interval 11.76 to 14.92	10.87 duration of response in months Interval 9.23 to 11.76

SECONDARY outcome

Timeframe: 45 months

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.	12.71 months Interval 11.3 to 14.06	8.54 months Interval 7.66 to 9.72

SECONDARY outcome

Timeframe: 12, 24 and 48 weeks

Population: Full Analysis Set

Higher values in the disease symptoms and side effects of treatment scores indicate worsening. Higher scores in the future perspective and body image scores indicate improvement. LS Means and SEM are estimated from the repeated measures model. Following factors and covariates are included in the repeated measurement model: time, treatment, treatment by time interaction, number of prior lines of anti-MM therapy (1/ 2 and 3), prior use of BTZ (Yes/ No), baseline score.Disease Symptom is the sum of 20 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-MY20 have the same score range of 0 -100. Decrease in symptom scores from baseline indicate improvement in symptoms.

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Disease Symptom wk 12 change baseline (n=215,243)	-4.795 score on a scale Interval -6.76 to -2.83	-4.865 score on a scale Interval -6.75 to -2.98
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Disease Symptom wk 24 change baseline (n=148,177)	-4.401 score on a scale Interval -6.53 to -2.27	-6.797 score on a scale Interval -8.79 to -4.81
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Disease Symptom wk 48 change baseline (n=37,26)	-2.836 score on a scale Interval -6.76 to -1.084	-6.626 score on a scale Interval -11.1 to -2.12
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Side effects of treatment wk 12 chge (n=213,242)	8.162 score on a scale Interval 6.51 to 9.814	5.524 score on a scale Interval 3.933 to 7.115
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Side effects of treatment wk 24 chge (n=148,175)	9.016 score on a scale Interval 6.955 to 11.08	7.731 score on a scale Interval 5.795 to 9.668
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Side effects of treatment wk 48 chge (n=37,26)	3.357 score on a scale Interval 0.442 to 6.273	3.654 score on a scale Interval 0.352 to 6.956
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Future perspective wk 12 chge (n=214,242)	5.319 score on a scale Interval 2.893 to 7.744	6.194 score on a scale Interval 3.854 to 8.533
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Future perspective wk 24 chge (n=148,176)	3.877 score on a scale Interval 0.977 to 6.778	5.839 score on a scale Interval 3.103 to 8.575
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Future perspective wk 48 chge (n=37,26)	4.331 score on a scale Interval -0.142 to 8.804	6.951 score on a scale Interval 1.807 to 12.1
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Body image wk 12 chge (n=213,240)	-7.178 score on a scale Interval -10.5 to -3.87	-6.22 score on a scale Interval -9.41 to -3.03
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Body image wk 24 chge (n=147,175)	-11.463 score on a scale Interval -15.3 to -7.66	-7.358 score on a scale Interval -10.9 to -3.81
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group Body image wk 48 chge (n=37,26)	-2.161 score on a scale Interval -7.73 to 3.41	-4.666 score on a scale Interval -11.1 to 1.729

SECONDARY outcome

Timeframe: 12, 24 and 48 weeks

Population: Full Analysis Set

The EORTC QLQ-C30 measures functional dimensions (physical, role, emotional, cognitive, and social), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), six single-item symptom scales (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Disease Symptom is the sum of 30 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-C30 have the same score range of 0 -100. For global health status and other functional scales,an increase from baseline indicates improvement of QoL. Whereas for symptoms scales, fatigue, dyspnea, insomnia, appetite loss, constipation and diarrhea, decrease in scores from baseline indicate improvement in symptoms.

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Insomnia wk 12 chge (n=216,239)	6.283 score on a scale Interval 2.851 to 9.715	7.625 score on a scale Interval 4.331 to 10.92
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Constipation wk 12 chge (n=215,240)	4.135 score on a scale Interval 0.667 to 7.603	6.42 score on a scale Interval 3.104 to 9.735
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Diarrhea wk 48 chge (n=38,26)	20.48 score on a scale Interval 14.02 to 26.94	10.996 score on a scale Interval 3.422 to 18.57
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Global health wk 12 change baseline (n=216,239)	-9.853 score on a scale Interval -12.5 to -7.2	-4.044 score on a scale Interval -6.6 to -1.49
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Global health wk 24 change baseline (n=150,176)	-7.867 score on a scale Interval -10.7 to -5.08	-1.518 score on a scale Interval -4.11 to -1.075
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Global health wk 48 change baseline (n=38,26)	-2.986 score on a scale Interval -7.21 to 1.237	4.345 score on a scale Interval -0.416 to 9.106
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Physical functioning wk 12 chge (n=217,242)	-9.67 score on a scale Interval -12.0 to -7.38	-5.393 score on a scale Interval -76.3 to -3.16
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Physical functioning wk 24 chge (n=151,177)	-9.516 score on a scale Interval -12.2 to -7.38	-6.456 score on a scale Interval -8.98 to -3.93
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Physical functioning wk 48 chge (n=38,26)	-2.88 score on a scale Interval -6.41 to 0.651	2.037 score on a scale Interval -2.07 to 6.147
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Role functioning wk 12 chge (n=215,237)	-11.159 score on a scale Interval -14.6 to -7.74	-6.762 score on a scale Interval -10.1 to -3.45
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Role functioning wk 24 chge (n=150,176)	-11.875 score on a scale Interval -15.7 to -8.01	-11.263 score on a scale Interval -14.9 to -7.61
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Role functioning wk 48 chge (n=38,26)	-5.927 score on a scale Interval -11.4 to -0.424	-0.401 score on a scale Interval -6.73 to 5.924
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Cognitive functioning wk 12 chge (n=216,240)	-4.464 score on a scale Interval -6.89 to -2.04	-1.023 score on a scale Interval -3.36 to 1.318
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Cognitive functioning wk 24 chge (n=149,176)	-6.053 score on a scale Interval -8.87 to -3.24	-3.542 score on a scale Interval -6.22 to -0.865
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Cognitive functioning wk 48 chge (n=38,26)	-5.568 score on a scale Interval -9.79 to -1.34	-4.042 score on a scale Interval -8.99 to 0.902
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Social functioning wk 12 chge (n=216,240)	-8.502 score on a scale Interval -11.6 to -5.44	-3.991 score on a scale Interval -6.97 to 1.02
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Social functioning wk 24 chge (n=148,171)	-8.925 score on a scale Interval -12.4 to -5.42	-6.338 score on a scale Interval -9.66 to -3.02
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Social functioning wk 48 chge (n=37,26)	-6.104 score on a scale Interval -11.0 to -1.22	4.617 score on a scale Interval -0.93 to 10.16
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Fatigue wk 12 chge (n=217,241)	15.122 score on a scale Interval 12.27 to 17.98	7.939 score on a scale Interval 5.174 to 10.7
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Fatigue wk 24 chge (n=151,176)	12.677 score on a scale Interval 9.419 to 15.94	9.203 score on a scale Interval 6.136 to 12.27
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Fatigue wk 48 chge(n=38,26)	4.646 score on a scale Interval 0.086 to 9.206	-2.625 score on a scale Interval -7.88 to 2.628
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Dyspnea wk 12 chge (n=217,240)	13.964 score on a scale Interval 10.6 to 17.33	6.266 score on a scale Interval 3.012 to 9.521
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Dyspnea wk 24 chge (n=151,177)	7.939 score on a scale Interval 4.639 to 11.24	5.308 score on a scale Interval 2.221 to 8.394
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Dyspnea wk 48 chge (n=38,26)	4.118 score on a scale Interval -1.58 to 9.813	2.82 score on a scale Interval -3.88 to 9.523
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Insomnia wk 24 chge (n=149,176)	10.023 score on a scale Interval 6.038 to 14.01	6.104 score on a scale Interval 2.381 to 9.827
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Insomnia wk 48 chge (n=38,26)	-2.464 score on a scale Interval -8.74 to 3.811	-3.442 score on a scale Interval -10.9 to 4.017
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Appetite loss wk 12 chge (n=217,239)	15.167 score on a scale Interval 11.6 to 18.74	5.383 score on a scale Interval 1.925 to 8.841
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Appetite loss wk 24 chge (n=151,176)	16.574 score on a scale Interval 12.39 to 20.76	5.861 score on a scale Interval 1.918 to 9.804
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Appetite loss wk 48 chge (n=38,26)	3.999 score on a scale Interval -2.08 to 10.07	-2.963 score on a scale Interval -9.99 to 4.061
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Constipation wk 24 chge (n=151,177)	-0.153 score on a scale Interval -3.64 to 3.337	0.524 score on a scale Interval -2.73 to 5.782
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Constipation wk 48 chge (n=38,25)	-0.358 score on a scale Interval -5.57 to 4.851	-0.946 score on a scale Interval -7.26 to 5.373
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Diarrhea wk 12 chge (n=217,241)	18.888 score on a scale Interval 15.04 to 22.74	10.206 score on a scale Interval 6.452 to 13.96
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group Diarrhea wk 24 chge (n=150,177)	23.163 score on a scale Interval 18.46 to 27.87	16.406 score on a scale Interval 11.98 to 20.83

SECONDARY outcome

Timeframe: 12, 24 and 48 weeks

Population: Full Analysis Set

Chronic Illness Therapy (FACIT) Measurement System and focuses on four general quality of life domains for physical well being, functional well-being, social/family well-being, and emotional well-being, and includes additional items to characterize treatment-related neurotoxicity. Higher subscales/total scores represent higher QOL. In the case of the neurotoxicity subscale, lower scores correspond to higher neurotoxicity. The recall period referenced in the questionnaire is the past 7 days.Ranges for FACT-G subscales are as follows:.PWB, scale 0 -28, , NtxS scale 0-44, FACT/GOG-Ntx trial outcome index scale is 0-100 and FACT-G scale is also scaled 0-100. An increase from baseline in these scores indicate improvement.

Outcome measures

Outcome measures
Measure	Panobinostat + Bortezomib n=387 Participants Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo + Bortezomib n=381 Participants Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Neurotoxicity wk 48 change baseline (n=35,26)	-3.158 score on a scale Interval -4.52 to -1.79	-2.133 score on a scale Interval -3.64 to -0.627
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Physical wellbeingwk 24 chge (n=150,176)	-3.044 score on a scale Interval -3.74 to -2.35	-2.259 score on a scale Interval -2.92 to -1.6
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Neurotoxicity wk 12 change baseline (n=212,240)	-4.481 score on a scale Interval -5.33 to -3.63	-3.337 score on a scale Interval -4.17 to -2.5
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Neurotoxicity wk 24 change baseline (n=148,174)	-4.564 score on a scale Interval -5.49 to -3.64	-4.739 score on a scale Interval -5.61 to -3.86
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Physical wellbeing wk 12 chge (n=215,240)	-3.29 score on a scale Interval -3.94 to -2.64	-1.952 score on a scale Interval -2.58 to -1.32
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Physical wellbeing wk 48 chge (n=38,26)	-2.037 score on a scale Interval -3.08 to -0.992	0.203 score on a scale Interval -1.03 to 1.439
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Trial Outcomes wk 12 chge (n=209,236)	-10.573 score on a scale Interval -12.2 to -8.86	-6.874 score on a scale Interval -8.55 to -5.19
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Trial Outcomes wk 24 chge (n=148,173)	-9.84 score on a scale Interval -11.7 to -7.98	-8.894 score on a scale Interval -10.7 to -7.13
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group Trial Outcomes wk 48 chge (n=35,26)	-6.633 score on a scale Interval -9.28 to -3.98	-2.821 score on a scale Interval -5.76 to 0.122
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT-G Total wk 12 chge (n=213,240)	-6.658 score on a scale Interval -8.23 to -5.09	-4.106 score on a scale Interval -5.64 to -2.57
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT-G Totalwk 24 chge (n=147,175)	-6.076 score on a scale Interval -7.84 to -4.31	-4.609 score on a scale Interval -6.3 to -2.92
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT-G Total wk 48 chge (n=37,26)	-2.704 score on a scale Interval -5.29 to -0.118	-1.435 score on a scale Interval -4.42 to 1.547
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT/GOGNTX Total wk 12 chge (n=206,230)	-11.176 score on a scale Interval -13.3 to -9.03	-7.524 score on a scale Interval -9.64 to -5.41
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT/GOGNTX Total wk 24 chge (n=146,172)	-10.581 score on a scale Interval -12.9 to -8.23	-9.179 score on a scale Interval -9.64 to -5.41
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group FACT/GOGNTX Total wk 48 chge (n=35,26)	-5.871 score on a scale Interval -9.24 to -2.5	-3.151 score on a scale Interval -6.92 to 0.614

Adverse Events

PAN+BTZ

Serious events: 228 serious events

Other events: 379 other events

Deaths: 0 deaths

PBO+BTZ

Serious events: 157 serious events

Other events: 366 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	PAN+BTZ n=381 participants at risk Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	PBO+BTZ n=377 participants at risk Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day..
Nervous system disorders Autonomic neuropathy	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Nervous system disorders Brain compression	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Anaemia	3.7% 14/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.80% 3/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Febrile neutropenia	0.79% 3/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Hyperviscosity syndrome	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Leukocytosis	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Leukopenia	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Monocytosis	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Neutropenia	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Pancytopenia	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Thrombocytopenia	7.3% 28/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	2.1% 8/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Acute coronary syndrome	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Acute myocardial infarction	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Angina pectoris	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.53% 2/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Atrial fibrillation	1.0% 4/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.53% 2/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Atrial flutter	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Bradycardia	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardiac arrest	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.53% 2/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardiac failure	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardiac failure acute	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardiac failure congestive	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardio-respiratory arrest	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Cardiopulmonary failure	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Left ventricular dysfunction	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Myocardial infarction	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Myocardial ischaemia	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Pericardial effusion	0.00% 0/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.27% 1/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Sinus tachycardia	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Tachycardia	0.52% 2/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Cardiac disorders Ventricular tachycardia	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Ear and labyrinth disorders Vertigo	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Eye disorders Conjunctivitis	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Eye disorders Exophthalmos	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Eye disorders Optic ischaemic neuropathy	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal discomfort	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal distension	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal pain	0.79% 3/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.80% 3/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal pain upper	0.26% 1/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Colitis	0.79% 3/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.00% 0/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Constipation	0.79% 3/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	0.80% 3/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex

Other adverse events
Measure	PAN+BTZ n=381 participants at risk Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	PBO+BTZ n=377 participants at risk Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day..
Blood and lymphatic system disorders Anaemia	40.4% 154/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	33.2% 125/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Leukopenia	16.0% 61/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	8.2% 31/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Lymphopenia	13.6% 52/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	9.3% 35/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Neutropenia	29.4% 112/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	10.6% 40/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Blood and lymphatic system disorders Thrombocytopenia	62.5% 238/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	39.8% 150/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Eye disorders Conjunctivitis	7.3% 28/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	8.2% 31/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal distension	7.9% 30/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	6.6% 25/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal pain	13.1% 50/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	10.1% 38/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Abdominal pain upper	11.3% 43/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	9.5% 36/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Constipation	26.5% 101/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	32.4% 122/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Diarrhoea	66.7% 254/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	41.1% 155/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Dyspepsia	12.3% 47/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	11.4% 43/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Nausea	36.0% 137/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	20.7% 78/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Gastrointestinal disorders Vomiting	23.9% 91/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	12.5% 47/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
General disorders Asthenia	20.2% 77/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	13.5% 51/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
General disorders Fatigue	40.7% 155/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	28.9% 109/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
General disorders Oedema peripheral	28.3% 108/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	19.1% 72/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
General disorders Pyrexia	23.6% 90/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	12.7% 48/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Bronchitis	5.2% 20/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	6.6% 25/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Herpes zoster	3.9% 15/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	9.5% 36/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Nasopharyngitis	12.9% 49/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	12.2% 46/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Respiratory tract infection	4.5% 17/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	5.3% 20/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Upper respiratory tract infection	17.1% 65/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	14.1% 53/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Infections and infestations Urinary tract infection	6.0% 23/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	4.0% 15/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Investigations Alanine aminotransferase increased	5.8% 22/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	5.0% 19/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Investigations Blood creatinine increased	9.7% 37/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	5.6% 21/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Investigations Blood urea increased	5.2% 20/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	2.7% 10/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Investigations Platelet count decreased	11.3% 43/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	4.5% 17/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Investigations Weight decreased	11.5% 44/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	4.5% 17/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Decreased appetite	27.8% 106/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	12.2% 46/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hyperglycaemia	7.9% 30/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	6.6% 25/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hypoalbuminaemia	5.5% 21/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	2.1% 8/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hypocalcaemia	9.2% 35/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	8.5% 32/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hypokalaemia	26.2% 100/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	13.8% 52/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hyponatraemia	12.6% 48/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	4.8% 18/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Metabolism and nutrition disorders Hypophosphataemia	11.0% 42/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	8.5% 32/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Musculoskeletal and connective tissue disorders Arthralgia	6.6% 25/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	6.9% 26/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Musculoskeletal and connective tissue disorders Back pain	11.8% 45/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	12.2% 46/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Musculoskeletal and connective tissue disorders Bone pain	5.5% 21/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	8.2% 31/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Musculoskeletal and connective tissue disorders Muscle spasms	6.0% 23/381 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex	5.6% 21/377 • Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex