Trial Outcomes & Findings for Phase 3 Study to Evaluate the Efficacy & Safety of Tralokinumab in Adults & Adolescents With OCS Dependent Asthma (NCT NCT02281357)

Last Updated: 2019-03-15

Results Overview

The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. Criteria used to assess asthma control included lung function assessments (forced expiratory volume in 1 second and morning peak expiratory flow), night awakenings, and the use of rescue medication and systemic corticosteroids. The least squares (LS) mean percent change from baseline in average daily OCS dose is presented. The final daily percent change from baseline was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}\*100%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

140 participants

Primary outcome timeframe

Baseline (Week 0) and Week 40

Results posted on

2019-03-15

Participant Flow

First patient enrolled: 19 February 2015; Last patient last visit: 07 September 2017. Study performed at 56 sites in 7 countries. Patients were maintained on their currently prescribed inhaled corticosteroid long-acting β2-agonist therapy and any additional asthma controller medications throughout the study period.

218 patients were screened. Prior to randomisation, patients completed a run-in period or run-in/oral corticosteroid (OCS) optimisation period (reached their minimum effective dose of OCS and remained stable on that dose for 2 weeks). 140 patients were randomised to study treatment. All randomised patients received study treatment.

Participant milestones

Participant milestones
Measure	Tralokinumab Tralokinumab 300 milligrams (mg) administered by subcutaneous (SC) injection every two weeks (Q2W) over a 40-week treatment period.	Placebo Placebo was administered by SC injection over a 40-week treatment period.
Overall Study STARTED	70	70
Overall Study COMPLETED	63	66
Overall Study NOT COMPLETED	7	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Tralokinumab Tralokinumab 300 milligrams (mg) administered by subcutaneous (SC) injection every two weeks (Q2W) over a 40-week treatment period.	Placebo Placebo was administered by SC injection over a 40-week treatment period.
Overall Study Adverse Event	2	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	4	3

Baseline Characteristics

Phase 3 Study to Evaluate the Efficacy & Safety of Tralokinumab in Adults & Adolescents With OCS Dependent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tralokinumab n=70 Participants Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 Participants Placebo was administered by SC injection over a 40-week treatment period.	Total n=140 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	58 Participants n=93 Participants	55 Participants n=4 Participants	113 Participants n=27 Participants
Age, Categorical >=65 years	11 Participants n=93 Participants	15 Participants n=4 Participants	26 Participants n=27 Participants
Age, Continuous	54.0 years STANDARD_DEVIATION 11.05 • n=93 Participants	55.4 years STANDARD_DEVIATION 10.26 • n=4 Participants	54.7 years STANDARD_DEVIATION 10.65 • n=27 Participants
Sex: Female, Male Female	48 Participants n=93 Participants	39 Participants n=4 Participants	87 Participants n=27 Participants
Sex: Female, Male Male	22 Participants n=93 Participants	31 Participants n=4 Participants	53 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	5 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) White	66 Participants n=93 Participants	63 Participants n=4 Participants	129 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 40

Population: The FAS included all randomised patients who received at least one dose of study treatment, irrespective of their protocol adherence and continued participation in the study.

Outcome measures

Outcome measures
Measure	Tralokinumab n=70 Participants Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 Participants Placebo was administered by SC injection over a 40-week treatment period.
Percent Change From Baseline in the Final Daily, Average, OCS Dose at Week 40 While Not Losing Asthma Control.	-37.62 Percent change from baseline Standard Error 4.98	-29.85 Percent change from baseline Standard Error 4.98

SECONDARY outcome

Timeframe: At Week 40

Population: The FAS included all randomised patients who received at least one dose of study treatment, irrespective of their protocol adherence and continued participation in the study.

The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with a final daily average OCS dose ≤5.0 mg is presented. For patients prescribed a fixed daily dose, then the average OCS dose was defined as the prescribed dose. For patients on a regimen where a different amount of OCS was to be taken each day, then the average OCS dose was defined as the average amount prescribed to be taken each day.

Outcome measures

Outcome measures
Measure	Tralokinumab n=70 Participants Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 Participants Placebo was administered by SC injection over a 40-week treatment period.
The Number of Patients With Final Daily Average OCS Dose ≤5 mg at Week 40.	32 Participants	28 Participants

SECONDARY outcome

Timeframe: At Week 40

Population: The FAS included all randomised patients who received at least one dose of study treatment, irrespective of their protocol adherence and continued participation in the study.

The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with ≥50% reduction in average daily OCS dose is presented. The final daily percent change from baseline was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}\*100%. If this resulted in a value of -50% or less (more negative), that patient was classified as having at least a 50% reduction in final daily average OCS dose.

Outcome measures

Outcome measures
Measure	Tralokinumab n=70 Participants Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 Participants Placebo was administered by SC injection over a 40-week treatment period.
The Number of Patients With ≥50% Reduction in Final Average Daily OCS Dose at Week 40.	31 Participants	26 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 40

Population: The FAS included all randomised patients who received at least one dose of study treatment, irrespective of their protocol adherence and continued participation in the study.

AAER up to Week 40 in the tralokinumab group was compared to that seen in the placebo group. The response variable was the number of exacerbations the patient experienced up to Week 40, with the logarithm of the time at risk in years of experiencing an exacerbation included as offset in the model. AAER = number of exacerbations\*365.25/(follow-up date - date of randomisation + 1). Asthma exacerbation was defined as a worsening of asthma that led to any of the following: * Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. * An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for \<24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids. * An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma.

Outcome measures

Outcome measures
Measure	Tralokinumab n=70 Participants Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 Participants Placebo was administered by SC injection over a 40-week treatment period.
Annual Asthma Exacerbation Rate (AAER) up to Week 40.	1.84 Adjusted rate (events/year) Interval 1.43 to 2.36	2.31 Adjusted rate (events/year) Interval 1.83 to 2.92

Adverse Events

Tralo 300 mg Q2W

Serious events: 9 serious events

Other events: 55 other events

Deaths: 0 deaths

Placebo

Serious events: 16 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: +1 301-398-0582

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Tralo 300 mg Q2W n=70 participants at risk Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 participants at risk Placebo was administered by SC injection over a 40-week treatment period.
Gastrointestinal disorders Colitis	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Bronchitis	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Influenza	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Injury, poisoning and procedural complications Hand fracture	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Investigations Pulmonary function test abnormal	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Investigations Weight decreased	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Tendonitis	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	7.1% 5/70 • Number of events 5 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	11.4% 8/70 • Number of events 12 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.

Measure	Tralo 300 mg Q2W n=70 participants at risk Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.	Placebo n=70 participants at risk Placebo was administered by SC injection over a 40-week treatment period.
General disorders Fatigue	4.3% 3/70 • Number of events 3 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	7.1% 5/70 • Number of events 6 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
General disorders Injection site erythema	8.6% 6/70 • Number of events 13 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
General disorders Injection site pain	8.6% 6/70 • Number of events 12 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
General disorders Injection site pruritus	7.1% 5/70 • Number of events 6 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	0.00% 0/70 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Bronchitis	15.7% 11/70 • Number of events 12 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	22.9% 16/70 • Number of events 20 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Oral candidiasis	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	5.7% 4/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Sinusitis	7.1% 5/70 • Number of events 7 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	5.7% 4/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	5.7% 4/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Infections and infestations Viral upper respiratory tract infection	35.7% 25/70 • Number of events 33 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	14.3% 10/70 • Number of events 12 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 2/70 • Number of events 3 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	8.6% 6/70 • Number of events 7 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	10.0% 7/70 • Number of events 7 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Nervous system disorders Headache	20.0% 14/70 • Number of events 33 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	15.7% 11/70 • Number of events 15 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	4.3% 3/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	12.9% 9/70 • Number of events 10 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.7% 4/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	1.4% 1/70 • Number of events 1 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.7% 4/70 • Number of events 5 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
Vascular disorders Hypertension	5.7% 4/70 • Number of events 4 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.	2.9% 2/70 • Number of events 2 • 40 weeks. Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.