Trial Outcomes & Findings for A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Patients With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome (NCT NCT01513317)

Last Updated: 2014-09-29

Results Overview

Reduction in RBC transfusions to treat the anemia of MDS is defined as a ≥50 percentage relative decrease and a ≥2 unit absolute decrease in RBC transfusions in the 8 weeks before the unblinding (scheduled to occur after 12 weeks of treatment) compared with RBC transfusions in the 8 weeks before the date the informed consent form was signed.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

Up to Week 13

Results posted on

2014-09-29

Participant Flow

76 participants were enrolled at 6 sites in Spain, 5 sites in the United States, 4 sites in Belgium, 3 sites each in Australia and the Russian Federation, 2 sites in the Netherlands, and 1 site in Sweden.

All 76 participants were enrolled and randomly assigned in the study.

Participant milestones

Participant milestones
Measure	Siltuximab 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Study STARTED	50	26
Overall Study COMPLETED	16	2
Overall Study NOT COMPLETED	34	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Siltuximab 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Overall Study Withdrawal by Subject	15	4
Overall Study Death	1	1
Overall Study Study terminated by sponsor	18	18
Overall Study Other	0	1

Baseline Characteristics

A Study Comparing Siltuximab Plus Best Supportive Care to Placebo Plus Best Supportive Care in Anemic Patients With International Prognostic Scoring System Low- or Intermediate-1-Risk Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Siltuximab n=50 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Total n=76 Participants Total of all reporting groups
Age, Continuous	70.2 years STANDARD_DEVIATION 7.7 • n=5 Participants	72 years STANDARD_DEVIATION 7.61 • n=7 Participants	70.8 years STANDARD_DEVIATION 7.67 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	9 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	17 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment Australia	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Belgium	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Russian Federation	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Spain	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Sweden	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	11 participants n=7 Participants	34 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 13

Population: Intent-to-treat population: Included all randomized participants

Outcome measures

Outcome measures
Measure	Siltuximab n=50 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Percentage of Participants Who Achieved a Reduction in Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS)	12 Percentage of participants	3.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Intent-to-treat population: Included all randomized participants with evaluable data at Week 13

Outcome measures

Outcome measures
Measure	Siltuximab n=31 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=18 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Change From Baseline in the Mean Hemoglobin Concentrations at Week 13	-0.07 g/dL Standard Deviation 1.503	-0.13 g/dL Standard Deviation 1.375

SECONDARY outcome

Timeframe: Week 13

Population: Intent-to-treat population: Included all randomized participants

Outcome measures

Outcome measures
Measure	Siltuximab n=50 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Percentage of Participants Achieving Hemoglobin Improvement (≥1.5 g/dL Increase From Baseline) Unrelated to Red Blood Cell (RBC) Transfusion at Week 13	8.0 Percentage of Participants	3.8 Percentage of Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Intent-to-treat population: Included all randomized participants

Outcome measures

Outcome measures
Measure	Siltuximab n=50 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Percentage of Participants Who Did Not Require a Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) in the 8 Weeks of Treatment Before Unblinding at Week 13	4.0 Percentage of Participants	3.8 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Intent-to-treat population: Included all randomized participants with evaluable data at Week 13

Outcome measures

Outcome measures
Measure	Siltuximab n=31 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=15 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Mean Changes From Baseline in Percentages of Bone Marrow Blast Cells at Week 13	2.1 Percentage of Bone Marrow Blast Cells Standard Deviation 8.22	0.2 Percentage of Bone Marrow Blast Cells Standard Deviation 2.08

SECONDARY outcome

Timeframe: 8 weeks

Population: Intent-to-treat population: Included all randomized participants who completed Week 13 unblinding

Outcome measures

Outcome measures
Measure	Siltuximab n=36 Participants 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=22 Participants Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Median Number of Red Blood Cell (RBC) Transfusions to Treat Anemia of Myelodysplastic Syndrome (MDS) During the 8 Weeks of Treatment Before Unblinding at Week 13	6.0 RBC Transfusions Interval 0.0 to 14.0	6.5 RBC Transfusions Interval 0.0 to 25.0

Adverse Events

Siltuximab

Serious events: 10 serious events

Other events: 30 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

DIRECTOR CLINICAL RESEARCH

Janssen Research & Development

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Siltuximab n=50 participants at risk 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 participants at risk Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Cardiac disorders Cardiac Failure Congestive	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Cardiac disorders Cardiovascular Insufficiency	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Cardiac disorders Ventricular Fibrillation	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Femoral Hernia	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Intestinal Ischaemia	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
General disorders Mucosal Haemorrhage	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Hepatobiliary disorders Cirrhosis Alcoholic	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Cellulitis	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Escherichia Bacteraemia	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Pneumonia	8.0% 4/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Sepsis	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Septic Shock	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Soft Tissue Infection	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Hip Fracture	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Vascular disorders Deep Vein Thrombosis	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Vascular disorders Peripheral Ischaemia	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.

Measure	Siltuximab n=50 participants at risk 15 mg/kg of siltuximab administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)	Placebo n=26 participants at risk Placebo administered as a 1-hour infusion every 4 weeks + best supportive care (BSC)
Blood and lymphatic system disorders Neutropenia	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal Pain Upper	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Constipation	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	15.4% 4/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	8.0% 4/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	11.5% 3/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	0.00% 0/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
General disorders Asthenia	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
General disorders Oedema Peripheral	16.0% 8/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Hepatobiliary disorders Hepatic Function Abnormal	10.0% 5/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	11.5% 3/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Infections and infestations Upper Respiratory Tract Infection	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	11.5% 3/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back Pain	12.0% 6/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Muscle Spasms	2.0% 1/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in Extremity	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	15.4% 4/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Dizziness	8.0% 4/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Headache	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	3.8% 1/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Insomnia	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	4.0% 2/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	15.4% 4/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.0% 4/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	7.7% 2/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.
Vascular disorders Hypotension	6.0% 3/50 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.	0.00% 0/26 • Adverse events are reported for the time period between the first dose of study medication through 30 days after the last dose. Safety was analyzed for all randomized participants who received at least 1 dose of study medication.