Trial Outcomes & Findings for Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer (NCT NCT00676663)

Last Updated: 2022-05-11

Results Overview

PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

130 participants

Primary outcome timeframe

From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)

Results posted on

2022-05-11

Participant Flow

Participants took part in the study at 38 investigative sites in the United States, Canada, Czech Republic, Hungary and Russia from 13 June 2008 to 26 November 2012.

Participants with a diagnosis of metastatic breast cancer were enrolled equally in one of two treatment arms: exemestane 25 mg plus entinostat 5 mg or exemestane 25 mg plus placebo.

Participant milestones

Participant milestones
Measure	Exemestane 25 mg + Placebo Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Overall Study STARTED	66	64
Overall Study COMPLETED	21	26
Overall Study NOT COMPLETED	45	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Exemestane 25 mg + Placebo Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Overall Study Death	43	27
Overall Study Withdrew Consent	1	8
Overall Study Lost to Follow-up	1	3

Baseline Characteristics

Height data is only available for n= 65, 63 participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=64 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Total n=130 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 10.06 • n=66 Participants	62.2 years STANDARD_DEVIATION 11.72 • n=64 Participants	62.4 years STANDARD_DEVIATION 10.87 • n=130 Participants
Age, Customized 18 to 44 years	2 Participants n=66 Participants	3 Participants n=64 Participants	5 Participants n=130 Participants
Age, Customized 45 to 64 years	38 Participants n=66 Participants	32 Participants n=64 Participants	70 Participants n=130 Participants
Age, Customized 65 to 74 years	19 Participants n=66 Participants	19 Participants n=64 Participants	38 Participants n=130 Participants
Age, Customized ≥75 years	7 Participants n=66 Participants	10 Participants n=64 Participants	17 Participants n=130 Participants
Sex: Female, Male Female	66 Participants n=66 Participants	64 Participants n=64 Participants	130 Participants n=130 Participants
Sex: Female, Male Male	0 Participants n=66 Participants	0 Participants n=64 Participants	0 Participants n=130 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=66 Participants	3 Participants n=64 Participants	4 Participants n=130 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	65 Participants n=66 Participants	61 Participants n=64 Participants	126 Participants n=130 Participants
Race/Ethnicity, Customized Black/African American	5 Participants n=66 Participants	4 Participants n=64 Participants	9 Participants n=130 Participants
Race/Ethnicity, Customized White	61 Participants n=66 Participants	60 Participants n=64 Participants	121 Participants n=130 Participants
Height	164.9 centimeters (cm) STANDARD_DEVIATION 6.38 • n=65 Participants • Height data is only available for n= 65, 63 participants.	162.7 centimeters (cm) STANDARD_DEVIATION 6.44 • n=63 Participants • Height data is only available for n= 65, 63 participants.	163.8 centimeters (cm) STANDARD_DEVIATION 6.48 • n=128 Participants • Height data is only available for n= 65, 63 participants.
Weight	73.2 kilograms (kg) STANDARD_DEVIATION 17.47 • n=66 Participants	75.6 kilograms (kg) STANDARD_DEVIATION 16.66 • n=64 Participants	74.3 kilograms (kg) STANDARD_DEVIATION 17.05 • n=130 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Score=0	50 Participants n=66 Participants	40 Participants n=64 Participants	90 Participants n=130 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Score=1	16 Participants n=66 Participants	24 Participants n=64 Participants	40 Participants n=130 Participants

PRIMARY outcome

Timeframe: From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)

Population: Full Analysis Set included all randomized participants.

PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause.

Outcome measures

Outcome measures
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=64 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Progression-free Survival (PFS)	2.27 months Interval 1.81 to 3.68	4.28 months Interval 3.26 to 5.36

SECONDARY outcome

Timeframe: From date of randomization to discontinuation due to disease progression or intolerable Adverse Event (AE) up to primary completion date (Median follow-up 6 months)

Population: Full Analysis Set included all randomized participants.

ORR is defined as the percentage of participants with response during treatment classified as complete response (CR) or partial response (PR), as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=64 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Objective Response Rate (ORR)	4.6 percentage of participants Interval 1.0 to 12.7	4.7 percentage of participants Interval 1.0 to 13.1

SECONDARY outcome

Timeframe: From date of randomization to discontinuation due to disease progression or intolerable AE up to primary completion date (Median follow-up 6 months)

Population: Full Analysis Set included all randomized participants.

CBR is defined as the percentage of participants with overall response (CR + PR) plus stable disease (SD) for 6 months as assessed by the investigator based on RECIST, version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=64 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Clinical Benefit Rate (CBR)	25.8 percentage of participants Interval 15.8 to 38.0	26.6 percentage of participants Interval 16.3 to 39.1

SECONDARY outcome

Timeframe: First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years)

Population: Safety Population included all randomized participants who received at least one dose of study drug.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. Abnormal clinical laboratory findings determined by the investigator to be clinically significant were recorded as AEs. A TEAE is an AE that starts after the administration of study drug. A SAE is any AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth effect or other significant medical hazard.

Outcome measures

Outcome measures
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=63 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAE	56 Participants	60 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAE	8 Participants	10 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First dose of study drug to end of study (Median follow-up 24 months in the EE arm and 26.4 months in the EP arm)

Population: Full Analysis Set included all randomized participants.

OS was defined as the number of months elapsed between the date of randomization and the date of death (whatever the cause).

Outcome measures

Outcome measures
Measure	Exemestane 25 mg + Placebo n=66 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=64 Participants Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Overall Survival (OS)	19.84 months Interval 17.04 to 26.71	28.13 months Interval 21.15 to Upper Confidence Interval was not estimable due to the low number of participants with events.

Adverse Events

Exemestane 25 mg + Placebo

Serious events: 8 serious events

Other events: 51 other events

Deaths: 0 deaths

Exemestane 25 mg + Entinostat 5 mg

Serious events: 10 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Kate Madigan, MD, Chief Medical Officer

Syndax Pharmaceuticals, Inc.

Phone: +1-858-888-3798

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of the results of the multi-center Study shall not be made before the first multi-site publication by Sponsor or Publications Committee. No Public Presentation by Institution or Investigator will be made until Study Documentation/Results from all sites are received and analyzed by Sponsor. Separate publication by Investigator will be delayed for a period of 18 months until the initial publication by Committee or Sponsor, or a determination is made not to make such publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Exemestane 25 mg + Placebo n=66 participants at risk Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Exemestane 25 mg + Entinostat 5 mg n=63 participants at risk Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
Blood and lymphatic system disorders Anemia group	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Lobar pneumonia	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	3.2% 2/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial tachycardia	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Enterocutaneous fistula	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Ileus	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia group	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Oesophagitis	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Overdose	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatic mass	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural nausea	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Radiation pneumonitis	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Sepsis	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia group	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Renal and urinary disorders Urinary tract infection	1.5% 1/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Vena cava thrombosis	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/66 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.	1.6% 1/63 • First dose to within 30 days of last dose of study drug (Up to approximately 2 Years) Safety population included all randomized participants who received at least 1 dose of study drug.