Trial Outcomes & Findings for CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma (NCT NCT00056160)

Last Updated: 2017-10-19

Results Overview

Time to progression (TTP) was calculated as the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et. al., Br J Haematol 1998; 102:1115-1123.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

353 participants

Primary outcome timeframe

60 weeks (median Time To Progression of CC-5013/Dex treatment group)

Results posted on

2017-10-19

Participant Flow

Subjects in the Placebo/Dex treatment group did not continue participation beyond the period "Up To Unblinding (07 Jun 2005"). Only subjects in the CC-5013/Dex treatment group participated in the period "Extended Follow-up Cutoff (23 Jul 2008)".

Only subjects in the CC-5013/Dex treatment group participated in the period "Extended Follow-up Cutoff (23 Jul 2008)". Data for the period "Extended Follow-up Cutoff (23 Jul 2008)" subsumes data for the period "Up To Unblinding (07 Jun 2005)".

Participant milestones

Participant milestones
Measure	CC-5013/Dex CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Up to Unblinding (07 Jun 2005) STARTED	177	176
Up to Unblinding (07 Jun 2005) COMPLETED	64	13
Up to Unblinding (07 Jun 2005) NOT COMPLETED	113	163
Extended Follow-up Cutoff (23 Jul 2008) STARTED	177	0
Extended Follow-up Cutoff (23 Jul 2008) COMPLETED	6	0
Extended Follow-up Cutoff (23 Jul 2008) NOT COMPLETED	171	0
Final Follow-up STARTED	6	0
Final Follow-up COMPLETED	0	0
Final Follow-up NOT COMPLETED	6	0

Reasons for withdrawal

Reasons for withdrawal
Measure	CC-5013/Dex CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Up to Unblinding (07 Jun 2005) Adverse Event	35	18
Up to Unblinding (07 Jun 2005) Progression of disease	57	124
Up to Unblinding (07 Jun 2005) Lack of Efficacy	3	5
Up to Unblinding (07 Jun 2005) Withdrawal by Subject	8	8
Up to Unblinding (07 Jun 2005) Death	2	1
Up to Unblinding (07 Jun 2005) Other	8	7
Extended Follow-up Cutoff (23 Jul 2008) Adverse Event	44	0
Extended Follow-up Cutoff (23 Jul 2008) Progression of disease	87	0
Extended Follow-up Cutoff (23 Jul 2008) Lack of Efficacy	3	0
Extended Follow-up Cutoff (23 Jul 2008) Withdrawal by Subject	11	0
Extended Follow-up Cutoff (23 Jul 2008) Death	5	0
Extended Follow-up Cutoff (23 Jul 2008) Other	21	0
Final Follow-up Transferred into expanded access study.	3	0
Final Follow-up Transferred into RevAssist Program	2	0
Final Follow-up Adverse Event	1	0

Baseline Characteristics

CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CC-5013/Dex n=177 Participants CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=176 Participants Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone	Total n=353 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	94 Participants n=5 Participants	103 Participants n=7 Participants	197 Participants n=5 Participants
Age, Categorical >=65 years	83 Participants n=5 Participants	73 Participants n=7 Participants	156 Participants n=5 Participants
Age, Continuous	63.3 years STANDARD_DEVIATION 9.84 • n=5 Participants	62.5 years STANDARD_DEVIATION 9.81 • n=7 Participants	62.9 years STANDARD_DEVIATION 9.81 • n=5 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	72 Participants n=7 Participants	143 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	104 Participants n=7 Participants	210 Participants n=5 Participants
Region of Enrollment United States	142 participants n=5 Participants	150 participants n=7 Participants	292 participants n=5 Participants
Region of Enrollment Canada	35 participants n=5 Participants	26 participants n=7 Participants	61 participants n=5 Participants

PRIMARY outcome

Timeframe: 60 weeks (median Time To Progression of CC-5013/Dex treatment group)

Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.

Outcome measures

Outcome measures
Measure	CC-5013/Dex n=177 Participants CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=176 Participants Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Time to Tumor Progression (TTP)	60.1 Weeks Interval 41.1 to 80.0	20.1 Weeks Interval 16.1 to 21.1

SECONDARY outcome

Timeframe: 170 weeks (median overall survival of CC-5013/Dex treatment group)

Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.

Overall survival was calculated as the time from randomization to death from any cause.

Outcome measures

Outcome measures
Measure	CC-5013/Dex n=177 Participants CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=176 Participants Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Overall Survival	170.1 Weeks Interval 142.1 to 204.9	136.4 Weeks Interval 104.1 to 176.9

SECONDARY outcome

Timeframe: Up to Unblinding (07 Jun 2005)

Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized. Results reported (Response) are numbers of subjects.

The overall confirmed response that was maintained for ≥6 weeks. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens.

Outcome measures

Outcome measures
Measure	CC-5013/Dex n=177 Participants CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=176 Participants Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Myeloma Response	107 Participants	34 Participants

SECONDARY outcome

Timeframe: 30 weeks (mean time to first worsening of ECOG performance status for CC-5013/Dex treatment group)

Population: Analysis conducted on the Intent-To-Treat (ITT) Population. The ITT Population was defined as all subjects randomized.

The time to first worsening on the ECOG Performance Scale was calculated as the time from randomization to the date of the first worsening compared to the last ECOG evaluation obtained prior to randomization.

Outcome measures

Outcome measures
Measure	CC-5013/Dex n=177 Participants CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=176 Participants Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.)	29.9 Weeks Standard Deviation 30.02	15.0 Weeks Standard Deviation 16.98

Adverse Events

CC-5013/Dex

Serious events: 111 serious events

Other events: 177 other events

Deaths: 0 deaths

Placebo/Dex

Serious events: 90 serious events

Other events: 175 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Robert Knight, M.D.

Celgene Corporation

Phone: 908-673-9749

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to publish and/or present the clinical data generated from the study provided that such Investigator shall furnish sponsor with a copy of the proposed publication or presentation at least 60 days in advance of submission, delete any confidential information, and delay submission for up to 90 days to permit the preparation and filing of appropriate intellectual property applications.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	CC-5013/Dex n=177 participants at risk CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=175 participants at risk Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Gastrointestinal disorders ABDOMINAL PAIN	1.7% 3/177 • Number of events 4 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations ABSCESS INTESTINAL	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations ABSCESS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Injury, poisoning and procedural complications ACETABULUM FRACTURE	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders ACQUIRED BRONCHOMALACIA	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	1.7% 3/177 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Endocrine disorders ADRENAL INSUFFICIENCY	1.1% 2/177 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Blood and lymphatic system disorders ANAEMIA	1.1% 2/177 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	1.7% 3/175 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations ANAL INFECTION	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders ANGINA PECTORIS	1.1% 2/177 • Number of events 2 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Psychiatric disorders ANXIETY	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Vascular disorders AORTIC STENOSIS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations APPENDICEAL ABSCESS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders APPENDICITIS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Vascular disorders ARTERIAL THROMBOSIS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders ARTERIOSPASM CORONARY	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations ARTHRITIS BACTERIAL	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
General disorders ASTHENIA	1.1% 2/177 • Number of events 2 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders ATRIAL FIBRILLATION	5.6% 10/177 • Number of events 11 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders ATRIAL FLUTTER	1.1% 2/177 • Number of events 2 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Renal and urinary disorders AZOTAEMIA	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Eye disorders BLINDNESS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Eye disorders BLINDNESS TRANSIENT	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Investigations BLOOD BILIRUBIN ABNORMAL	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Investigations BLOOD CREATININE INCREASED	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders BONE PAIN	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BRONCHIOLOALVEOLAR CARCINOMA	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders BRONCHITIS	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders BRONCHOSPASM	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders CARDIAC ARREST	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders CARDIAC FAILURE CONGESTIVE	2.3% 4/177 • Number of events 4 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Cardiac disorders CARDIO-RESPIRATORY ARREST	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Eye disorders CATARACT UNILATERAL	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations CATHETER RELATED INFECTION	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
General disorders CATHETER SITE PAIN	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations CELLULITIS	1.1% 2/177 • Number of events 2 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations CELLULITIS STAPHYLOCOCCAL	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders CEREBELLAR INFARCTION	0.56% 1/177 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders CEREBRAL INFARCTION	0.00% 0/177 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.

Other adverse events
Measure	CC-5013/Dex n=177 participants at risk CC-5013 (lenalidomide) plus oral high-dose dexamethasone	Placebo/Dex n=175 participants at risk Placebo, identical in appearance to CC-5013 (lenalidomide), plus oral high-dose dexamethasone
Gastrointestinal disorders ABDOMINAL DISTENSION	6.2% 11/177 • Number of events 12 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	8.6% 15/175 • Number of events 18 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders ABDOMINAL PAIN	11.3% 20/177 • Number of events 27 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	6.9% 12/175 • Number of events 15 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	6.2% 11/177 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	5.7% 10/175 • Number of events 12 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders AGEUSIA	5.6% 10/177 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	4.0% 7/175 • Number of events 7 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Blood and lymphatic system disorders ANAEMIA	40.7% 72/177 • Number of events 139 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	21.1% 37/175 • Number of events 44 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Metabolism and nutrition disorders ANOREXIA	19.8% 35/177 • Number of events 39 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	12.6% 22/175 • Number of events 23 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Psychiatric disorders ANXIETY	18.1% 32/177 • Number of events 38 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	11.4% 20/175 • Number of events 22 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Metabolism and nutrition disorders APPETITE DECREASED	11.9% 21/177 • Number of events 25 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	6.9% 12/175 • Number of events 14 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders ARTHRALGIA	23.2% 41/177 • Number of events 63 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	20.0% 35/175 • Number of events 51 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
General disorders ASTHENIA	24.3% 43/177 • Number of events 59 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	26.9% 47/175 • Number of events 66 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders BACK PAIN	32.2% 57/177 • Number of events 71 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	21.7% 38/175 • Number of events 40 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders BALANCE IMPAIRED	5.6% 10/177 • Number of events 11 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	1.7% 3/175 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Investigations BLOOD CREATININE INCREASED	5.1% 9/177 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	3.4% 6/175 • Number of events 6 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders BONE PAIN	11.3% 20/177 • Number of events 31 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	8.6% 15/175 • Number of events 25 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders BRONCHITIS	10.7% 19/177 • Number of events 24 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	1.7% 3/175 • Number of events 7 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Eye disorders CATARACT	5.1% 9/177 • Number of events 10 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Eye disorders CATARACT UNILATERAL	5.6% 10/177 • Number of events 15 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	1.1% 2/175 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Infections and infestations CELLULITIS	5.6% 10/177 • Number of events 11 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	1.7% 3/175 • Number of events 3 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
General disorders CHEST PAIN	12.4% 22/177 • Number of events 34 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	8.6% 15/175 • Number of events 24 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Musculoskeletal and connective tissue disorders CHEST WALL PAIN	9.6% 17/177 • Number of events 18 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	5.1% 9/175 • Number of events 9 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Psychiatric disorders CONFUSIONAL STATE	12.4% 22/177 • Number of events 25 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	8.0% 14/175 • Number of events 16 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders CONSTIPATION	41.8% 74/177 • Number of events 99 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	20.0% 35/175 • Number of events 43 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Skin and subcutaneous tissue disorders CONTUSION	11.3% 20/177 • Number of events 23 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	7.4% 13/175 • Number of events 15 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders COUGH	29.9% 53/177 • Number of events 91 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	27.4% 48/175 • Number of events 53 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Endocrine disorders CUSHINGOID	6.8% 12/177 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	7.4% 13/175 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Vascular disorders DEEP VEIN THROMBOSIS	5.6% 10/177 • Number of events 10 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.00% 0/175 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Metabolism and nutrition disorders DEHYDRATION	11.9% 21/177 • Number of events 26 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	5.1% 9/175 • Number of events 10 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Psychiatric disorders DEPRESSION	16.4% 29/177 • Number of events 31 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	10.9% 19/175 • Number of events 19 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders DIARRHOEA	48.0% 85/177 • Number of events 174 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	30.3% 53/175 • Number of events 85 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders DIZZINESS	28.8% 51/177 • Number of events 102 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	24.6% 43/175 • Number of events 54 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders DRY MOUTH	9.6% 17/177 • Number of events 18 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	4.6% 8/175 • Number of events 10 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Skin and subcutaneous tissue disorders DRY SKIN	10.7% 19/177 • Number of events 24 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	5.7% 10/175 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Nervous system disorders DYSGEUSIA	19.2% 34/177 • Number of events 37 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	10.9% 19/175 • Number of events 23 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Gastrointestinal disorders DYSPEPSIA	20.9% 37/177 • Number of events 41 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	16.0% 28/175 • Number of events 37 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders DYSPNOEA EXERTIONAL	7.9% 14/177 • Number of events 16 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	6.9% 12/175 • Number of events 12 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	28.8% 51/177 • Number of events 64 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	22.3% 39/175 • Number of events 47 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Skin and subcutaneous tissue disorders ECCHYMOSIS	5.1% 9/177 • Number of events 9 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	0.57% 1/175 • Number of events 1 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	9.0% 16/177 • Number of events 21 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	6.3% 11/175 • Number of events 12 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Skin and subcutaneous tissue disorders ERYTHEMA	5.6% 10/177 • Number of events 12 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	3.4% 6/175 • Number of events 6 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.
Skin and subcutaneous tissue disorders FACE OEDEMA	7.3% 13/177 • Number of events 15 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.	7.4% 13/175 • Number of events 13 • Up to 254 weeks (median=48 weeks; mean=77 weeks) Analyses of safety (Serious Adverse Events and Other Adverse Events) were based upon the Safety Population (all subjects who were administered at least one dose of study medication) and include all data available.