Trial Outcomes & Findings for Study of Safety of QAW039 in Patients With Asthma Inadequately Controlled on Standard-of-care Asthma Treatment (NCT NCT03052517)

Last Updated: 2020-10-12

Results Overview

Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs. For this Outcome Measure, AE up to week 52 are reported.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

2538 participants

Primary outcome timeframe

52 weeks

Results posted on

2020-10-12

Participant Flow

Participants were from ARG, AUS, AUT, BEL, BRA, BGR, CAN, CHN, COL, CZE, EST, FIN, FRA, DEU, GRC, GTM, HUN, IND, ISR, JPN, LVA, LBN, LTU, MYS, MEX, NLD, PER, PHL, POL, ROU, RUS, SAU, SRB, SGP, SVK, ESP, CHE, TWN, TUR, GBR, USA

Eligible patients included patients completing a prior QAW039 Phase 3 study (CQAW039A2307, QAW039A2314, CQAW039A2316, or CQAW039A2317) and patients who had not previously participated in a QAW039 study.

Participant milestones

Participant milestones
Measure	QAW039 150mg QAW039 Dose 1 once daily	QAW039 450 mg QAW039 Dose 2 once daily	Placebo Placebo once daily
Overall Study STARTED	1093	1085	360
Overall Study Safety Set (SAF)	1092	1084	361
Overall Study COMPLETED	76	71	32
Overall Study NOT COMPLETED	1017	1014	328

Reasons for withdrawal

Reasons for withdrawal
Measure	QAW039 150mg QAW039 Dose 1 once daily	QAW039 450 mg QAW039 Dose 2 once daily	Placebo Placebo once daily
Overall Study Study Terminated By Sponsor	928	938	296
Overall Study Subject/Guardian Decision	50	45	22
Overall Study Lack of Efficacy	23	14	7
Overall Study Adverse Event	6	5	0
Overall Study Physician Decision	4	5	1
Overall Study Death	3	0	1
Overall Study Lost to Follow-up	2	4	0
Overall Study Pregnancy	1	0	1
Overall Study Non-Compliance With Study Treatment	0	2	0
Overall Study Technical Problems	0	1	0

Baseline Characteristics

Study of Safety of QAW039 in Patients With Asthma Inadequately Controlled on Standard-of-care Asthma Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QAW039 150mg n=1092 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1084 Participants QAW039 Dose 2 once daily	Placebo n=361 Participants Placebo once daily	Total n=2537 Participants Total of all reporting groups
Age, Continuous	50.1 Years STANDARD_DEVIATION 14.95 • n=5 Participants	50.1 Years STANDARD_DEVIATION 15.55 • n=7 Participants	49.9 Years STANDARD_DEVIATION 14.99 • n=5 Participants	50.1 Years STANDARD_DEVIATION 15.21 • n=4 Participants
Sex: Female, Male Female	659 Participants n=5 Participants	666 Participants n=7 Participants	229 Participants n=5 Participants	1554 Participants n=4 Participants
Sex: Female, Male Male	433 Participants n=5 Participants	418 Participants n=7 Participants	132 Participants n=5 Participants	983 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	757 Participants n=5 Participants	756 Participants n=7 Participants	243 Participants n=5 Participants	1756 Participants n=4 Participants
Race/Ethnicity, Customized Black	30 Participants n=5 Participants	14 Participants n=7 Participants	11 Participants n=5 Participants	55 Participants n=4 Participants
Race/Ethnicity, Customized Asian	219 Participants n=5 Participants	215 Participants n=7 Participants	73 Participants n=5 Participants	507 Participants n=4 Participants
Race/Ethnicity, Customized Native American	27 Participants n=5 Participants	40 Participants n=7 Participants	12 Participants n=5 Participants	79 Participants n=4 Participants
Race/Ethnicity, Customized Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Other	59 Participants n=5 Participants	49 Participants n=7 Participants	20 Participants n=5 Participants	128 Participants n=4 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: Safety analysis set (SAF): included all patients who received at least one dose of study drug during this study. Patients were analyzed according to the treatment they received during this study. Only patients with data for all terms in the Cox regression model were included

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 52 - Cox Regression Model	675 Participants	654 Participants	237 Participants

PRIMARY outcome

Timeframe: 156 weeks

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 156 - Cox Regression Model	709 Participants	681 Participants	243 Participants

PRIMARY outcome

Timeframe: 52 weeks

Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs. For this Outcome Measure, AE up to week 52 are reported.

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 52 - Cox Regression Model	73 Participants	53 Participants	29 Participants

PRIMARY outcome

Timeframe: 156 weeks

Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs.

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 156 - Cox Regression Model	86 Participants	63 Participants	33 Participants

PRIMARY outcome

Timeframe: 52 weeks

Adverse events leading to study treatment discontinuation starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs leading to study treatment discontinuation. For this Outcome Measure, AE up to week 52 are reported.

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 52 - Cox Regression Model	26 Participants	33 Participants	9 Participants

PRIMARY outcome

Timeframe: 156 weeks

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 156 - Cox Regression Model	30 Participants	37 Participants	9 Participants

SECONDARY outcome

Timeframe: 52 weeks

The number of patients per patient year of follow-up having a treatment emergent adverse event, categorized by system organ class. Treatment emergent adverse events are defined as an AEs starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE)

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Number of patients with at least one AE	675 Participants	654 Participants	237 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Blood and lymphatic system disorders	21 Participants	10 Participants	5 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Cardiac disorders	11 Participants	26 Participants	7 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Congenital, familial and genetic disorders	1 Participants	3 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Ear and labyrinth disorders	16 Participants	9 Participants	8 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Endocrine disorders	2 Participants	6 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model General disorders & administration site conditions	38 Participants	33 Participants	7 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Hepatobiliary disorders	9 Participants	17 Participants	7 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Investigations	79 Participants	85 Participants	20 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Neoplasms benign, malignant and unspecified	13 Participants	9 Participants	3 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Nervous system disorders	67 Participants	73 Participants	29 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Psychiatric disorders	18 Participants	15 Participants	9 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Renal and urinary disorders	33 Participants	41 Participants	8 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Reproductive system and breast disorders	14 Participants	9 Participants	4 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Respiratory, thoracic and mediastinal disorders	308 Participants	304 Participants	135 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Skin and subcutaneous tissue disorders	38 Participants	39 Participants	13 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Social circumstances	1 Participants	1 Participants	3 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Eye disorders	13 Participants	11 Participants	9 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Gastrointestinal disorders	88 Participants	86 Participants	32 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Immune system disorders	11 Participants	10 Participants	6 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Infections and infestations	400 Participants	374 Participants	145 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Injury, poisoning and procedural complications	67 Participants	52 Participants	23 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Metabolism and nutrition disorders	53 Participants	50 Participants	21 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Musculoskeletal and connective tissue disorders	91 Participants	84 Participants	24 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Product issues	1 Participants	0 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model Vascular disorders	39 Participants	33 Participants	9 Participants

SECONDARY outcome

Timeframe: 156 weeks

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1081 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1077 Participants QAW039 Dose 2 once daily	Placebo n=359 Participants Placebo once daily
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Gastrointestinal disorders	101 Participants	96 Participants	38 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model General disorders & administration site conditions	43 Participants	34 Participants	8 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Hepatobiliary disorders	10 Participants	21 Participants	8 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Immune system disorders	11 Participants	11 Participants	6 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Infections and infestations	436 Participants	415 Participants	151 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Metabolism and nutrition disorders	61 Participants	60 Participants	23 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Reproductive system and breast disorders	17 Participants	10 Participants	4 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Vascular disorders	45 Participants	40 Participants	13 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Number of patients with at least one AE	710 Participants	682 Participants	243 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Blood and lymphatic system disorders	23 Participants	12 Participants	5 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Cardiac disorders	16 Participants	34 Participants	7 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Congenital, familial and genetic disorders	1 Participants	3 Participants	1 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Ear and labyrinth disorders	18 Participants	13 Participants	9 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Endocrine disorders	5 Participants	7 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Eye disorders	16 Participants	14 Participants	9 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Injury, poisoning and procedural complications	80 Participants	63 Participants	28 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Investigations	90 Participants	102 Participants	24 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Musculoskeletal and connective tissue disorders	102 Participants	92 Participants	31 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Neoplasms benign, malignant and unspecified	17 Participants	11 Participants	3 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Nervous system disorders	83 Participants	77 Participants	32 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Pregnancy, puerperium and perinatal conditions	1 Participants	0 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Product issues	1 Participants	0 Participants	0 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Psychiatric disorders	23 Participants	18 Participants	9 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Renal and urinary disorders	36 Participants	45 Participants	10 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Respiratory, thoracic and mediastinal disorders	336 Participants	341 Participants	144 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Skin and subcutaneous tissue disorders	45 Participants	45 Participants	15 Participants
Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model Social circumstances	1 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 52 weeks

The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1092 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1084 Participants QAW039 Dose 2 once daily	Placebo n=361 Participants Placebo once daily
Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 52	0 Number of deaths	0 Number of deaths	0 Number of deaths

SECONDARY outcome

Timeframe: 156 weeks

The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1092 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1084 Participants QAW039 Dose 2 once daily	Placebo n=361 Participants Placebo once daily
Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 156	0 Number of deaths	0 Number of deaths	0 Number of deaths

SECONDARY outcome

Timeframe: 52 weeks

Number of treatment emergent severe asthma exacerbation episodes requiring hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours) per person year of follow-up. Treatment emergent severe asthma exacerbation episodes are defined as episodes occurring on or after the day of the first intake of study drug and until the day of last intake of study drug +7 days (30 days in the case of a serious AE). Rate of exacerbations per person year = total number of exacerbations / total number of treatment years

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1092 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1084 Participants QAW039 Dose 2 once daily	Placebo n=361 Participants Placebo once daily
Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 52	0.04 Hospitalizations per person year	0.02 Hospitalizations per person year	0.06 Hospitalizations per person year

SECONDARY outcome

Timeframe: 156 weeks

Outcome measures

Outcome measures
Measure	QAW039 150mg n=1092 Participants QAW039 Dose 1 once daily	QAW039 450 mg n=1084 Participants QAW039 Dose 2 once daily	Placebo n=361 Participants Placebo once daily
Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 156	0.04 Hospitalizations per person year	0.02 Hospitalizations per person year	0.05 Hospitalizations per person year

Adverse Events

QAW039 150 mg

Serious events: 87 serious events

Other events: 525 other events

Deaths: 3 deaths

QAW039 450 mg

Serious events: 64 serious events

Other events: 499 other events

Deaths: 1 deaths

Placebo

Serious events: 33 serious events

Other events: 190 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	QAW039 150 mg n=1092 participants at risk QAW039 150 mg	QAW039 450 mg n=1084 participants at risk QAW039 450 mg	Placebo n=361 participants at risk Placebo
Infections and infestations Bronchitis	6.9% 75/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	5.1% 55/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	10.5% 38/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Influenza	2.7% 30/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.6% 28/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.5% 9/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Nasopharyngitis	10.1% 110/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	9.8% 106/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	10.0% 36/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Pharyngitis	3.1% 34/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.0% 22/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	4.2% 15/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Sinusitis	3.6% 39/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.6% 28/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.5% 9/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Upper respiratory tract infection	6.6% 72/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	4.0% 43/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	6.9% 25/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Upper respiratory tract infection bacterial	1.3% 14/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.9% 31/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.3% 12/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Urinary tract infection	2.1% 23/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.4% 37/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.0% 11/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Infections and infestations Viral upper respiratory tract infection	3.1% 34/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.9% 31/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.5% 9/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Investigations Blood creatinine increased	2.7% 30/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.9% 42/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	0.55% 2/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 22/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	1.0% 11/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.2% 8/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Musculoskeletal and connective tissue disorders Back pain	2.7% 29/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.9% 31/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.8% 10/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Nervous system disorders Headache	3.8% 41/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.7% 29/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	6.6% 24/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Respiratory, thoracic and mediastinal disorders Asthma	26.6% 291/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	25.4% 275/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	34.6% 125/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.7% 19/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.6% 28/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.0% 11/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).
Vascular disorders Hypertension	2.7% 30/1092 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	2.8% 30/1084 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).	3.0% 11/361 • Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks. Any sign or symptom that occurs during the study treatment plus the 7 days post treatment (30 days in the case of a serious AE).