Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02555683
• Collaborator: (none)
• Enrollment: 894
• Locations: 233
• Arms: 3
• Actual Duration (Months): 46.8
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study aimed to determine the efficacy and safety of QAW039 150 mg and QAW039 450 mg, compared with placebo, when added to GINA (Global Initiative for Asthma) steps 4 and 5 standard-of- care (SoC) asthma therapy (GINA 2016) in the following two populations:

• patient with inadequately controlled severe asthma and high eosinophil counts at baseline (eosinophil count at Visit 1 ≥250 cells/ µl) (sub-population)

• patients with inadequately controlled severe asthma (overall study population)

Inadequate control is defined as partly controlled or uncontrolled asthma (GINA 2016).

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QAW039; Drug: QAW039; Drug: Placebo	Phase 3

Detailed Description

This study used a randomized, multicenter, double-blind, placebo-controlled parallel-group design in which QAW039 150 mg or QA039 450 mg or placebo was added to standard of care, GINA steps 4 and 5 asthma therapy.

The study included:

• Screening period of up to 2 weeks to assess eligibility;

• Run-in period of approximately 2 weeks and a maximum of 6 weeks on placebo to collect baseline data for efficacy variables and compliance with the Electronic Peak Flow/ eDiary device. Upon completion of the run-in period, all patients who met the eligibility criteria were randomized to one of three treatments: QAW039 150 mg or QAW039 450 mg or placebo once daily in a ratio of 1:1:1.

• Treatment period of 52 weeks (assessment period for all Primary and Secondary Outcome Measures). Clinic visits were scheduled approximately 4 weeks after randomization and then at approximately 8-week intervals during the active-treatment period. Phone calls occurred at specified time points between visits occurring at 8-week intervals. Patients who had successfully completed 52 weeks of treatment in this study were offered an optional participation in a safety study (CQAW039A2315).

• Follow-up period of 4 weeks, investigational and drug-free, following the last dose of study drug. A follow-up visit occurred approximately 4 weeks (i.e., approximately 30 days) following the last dose of study therapy to complete safety assessments and pregnancy testing (if applicable). the follow-up period applied to all patients except those patients who had entered the safety study (CQAW039A2315) directly after the Week 52 study visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 894 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 When Added to Existing Asthma Therapy in Patients With Uncontrolled Severe Asthma.
• Actual Study Start Date: Dec 11, 2015
• Actual Primary Completion Date: Oct 21, 2019
• Actual Study Completion Date: Nov 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QAW039 150 mg QAW039 150 mg once daily	Drug: QAW039; QAW039 150 mg once daily
Experimental: QAW039 450 mg QAW039 450 mg once daily	Drug: QAW039; QAW039 450 mg once daily
Placebo Comparator: Placebo Placebo once daily	Drug: Placebo; Placebo once daily

Outcome Measures

Primary Outcome Measures

1. Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation [Baseline, Week 52]

   A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

2. Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population [Baseline, Week 52]

   A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).

Secondary Outcome Measures

1. Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in High Eosinophils Subpopulation [52 weeks]

   The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

2. Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in High Eosinophils Subpopulation [Baseline, Week 52]

   The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

3. Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation [Baseline, Week 52]

   Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.

4. Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population [Baseline, Week 52]

   The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life.

5. Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in Overall Population [Baseline, Week 52]

   The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).

6. Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population [Baseline, Week 52]

   Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent and assent (if applicable).

• Male and female patients aged ≥12 years (or ≥lower age limit allowed by health authority and/or ethics committee/institutional review board approvals).

• A diagnosis of severe asthma, uncontrolled on GINA 4/5 asthma medication.

• Evidence of airway reversibility or airway hyper- reactivity.

• FEV1 of ≤80% of the predicted normal value for patients aged ≥18 years; FEV1 of ≤90% for patients aged 12 to <18 years

• An ACQ score ≥1.5.

• A history of 2 or more asthma exacerbations within the 12 months prior to entering the study.

Exclusion Criteria:

• Use of other investigational drugs within 5 half-lives of study entry, or within 30 days, whichever is longer.

• Subjects who have participated in another trial of QAW039.

• A QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female).

• History of malignancy with the exception of local basal cell carcinoma of the skin.

• Pregnant or nursing (lactating) women.

• Serious co-morbidities.

• Patients on greater than 20 mg of simvastatin, greater than 40 mg of atorvastatin, greater than 40 mg of pravastatin, or greater than 2 mg of pitavastatin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35209
2	Novartis Investigative Site	Birmingham	Alabama	United States	35249
3	Novartis Investigative Site	Gilbert	Arizona	United States	85234
4	Novartis Investigative Site	Litchfield Park	Arizona	United States	85340
5	Novartis Investigative Site	Peoria	Arizona	United States	85381
6	Novartis Investigative Site	Little Rock	Arkansas	United States	72209
7	Novartis Investigative Site	Hawaiian Gardens	California	United States	90716
8	Novartis Investigative Site	Newport Beach	California	United States	92663
9	Novartis Investigative Site	Redondo Beach	California	United States	90277
10	Novartis Investigative Site	Riverside	California	United States	92506
11	Novartis Investigative Site	Torrance	California	United States	90503
12	Novartis Investigative Site	Westminster	California	United States	92683
13	Novartis Investigative Site	New Haven	Connecticut	United States	06520
14	Novartis Investigative Site	Brandon	Florida	United States	33511
15	Novartis Investigative Site	New Smyrna Beach	Florida	United States	32168
16	Novartis Investigative Site	Orlando	Florida	United States	32803
17	Novartis Investigative Site	Orlando	Florida	United States	32806
18	Novartis Investigative Site	Ormond Beach	Florida	United States	32174
19	Novartis Investigative Site	Sebring	Florida	United States	33870
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98	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
99	Novartis Investigative Site	Nanchang	Jiangxi	China	330006
100	Novartis Investigative Site	Chang Chun	Jilin	China	130021
101	Novartis Investigative Site	Shenyang	Liaoning	China	110000
102	Novartis Investigative Site	Shenyang	Liaoning	China	110003
103	Novartis Investigative Site	Xian	Shanxi	China	710061
104	Novartis Investigative Site	Chengdu	Sichuan	China	610041
105	Novartis Investigative Site	Hangzhou	Zhejiang	China	310014
106	Novartis Investigative Site	Beijing		China	100050
107	Novartis Investigative Site	Chengdu		China	610083
108	Novartis Investigative Site	Chongqing		China	400037
109	Novartis Investigative Site	Shanghai		China	200433
110	Novartis Investigative Site	Tianjin		China	300052
111	Novartis Investigative Site	Copenhagen NV		Denmark	2400
112	Novartis Investigative Site	Tallinn		Estonia	13419
113	Novartis Investigative Site	Tallinn		Estonia	13619
114	Novartis Investigative Site	Tartu		Estonia	51014
115	Novartis Investigative Site	Helsinki		Finland	00290
116	Novartis Investigative Site	HUS		Finland	00029
117	Novartis Investigative Site	OYS		Finland	FIN-90029
118	Novartis Investigative Site	Tampere		Finland	33520
119	Novartis Investigative Site	Montpellier cedex 5	Herault	France	34059
120	Novartis Investigative Site	Dijon		France	21000
121	Novartis Investigative Site	Le Kremlin Bicetre		France	94275
122	Novartis Investigative Site	Lyon Cedex 04		France	69317
123	Novartis Investigative Site	Marseille		France	13015
124	Novartis Investigative Site	Nantes		France	44093
125	Novartis Investigative Site	Paris		France	75018
126	Novartis Investigative Site	Reims Cedex		France	51092
127	Novartis Investigative Site	Strasbourg Cedex		France	67091
128	Novartis Investigative Site	Heidelberg	Baden-Württemberg	Germany	69126
129	Novartis Investigative Site	Berlin		Germany	10717
130	Novartis Investigative Site	Berlin		Germany	10969
131	Novartis Investigative Site	Berlin		Germany	12159
132	Novartis Investigative Site	Berlin		Germany	12203
133	Novartis Investigative Site	Berlin		Germany	12627
134	Novartis Investigative Site	Berlin		Germany	13187
135	Novartis Investigative Site	Frankfurt		Germany	60313
136	Novartis Investigative Site	Frankfurt		Germany	60389
137	Novartis Investigative Site	Frankfurt		Germany	60596
138	Novartis Investigative Site	Halle		Germany	06108
139	Novartis Investigative Site	Hamburg		Germany	20354
140	Novartis Investigative Site	Landsberg		Germany	86899
141	Novartis Investigative Site	Leipzig		Germany	04103
142	Novartis Investigative Site	Leipzig		Germany	04357
143	Novartis Investigative Site	Magdeburg		Germany	39120
144	Novartis Investigative Site	Mainz		Germany	55131
145	Novartis Investigative Site	Marburg		Germany	D-35037
146	Novartis Investigative Site	Neu Isenburg		Germany	63263
147	Novartis Investigative Site	Rosenheim		Germany	83026
148	Novartis Investigative Site	Rostock		Germany	18057
149	Novartis Investigative Site	Rudersdorf		Germany	15562
150	Novartis Investigative Site	Witten		Germany	58452
151	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
152	Novartis Investigative Site	Ciudad	Gautemala	Guatemala	01010
153	Novartis Investigative Site	Guatemala City	GTM	Guatemala	01010
154	Novartis Investigative Site	Guatemala City	GTM	Guatemala	01011
155	Novartis Investigative Site	Guatemala City		Guatemala	01010
156	Novartis Investigative Site	Guatemala City		Guatemala	01011
157	Novartis Investigative Site	Eger	HUN	Hungary	3300
158	Novartis Investigative Site	Gyor	HUN	Hungary	9024
159	Novartis Investigative Site	Hajdunanas	HUN	Hungary	4080
160	Novartis Investigative Site	Mako	HUN	Hungary	6900
161	Novartis Investigative Site	Szazhalombatta	HUN	Hungary	2440
162	Novartis Investigative Site	Torokbalint	Pest	Hungary	2045
163	Novartis Investigative Site	Komarom		Hungary	2900
164	Novartis Investigative Site	Pecs		Hungary	7635
165	Novartis Investigative Site	Reykjavik		Iceland	109
166	Novartis Investigative Site	Dublin		Ireland	24
167	Novartis Investigative Site	Dublin		Ireland	DUBLIN 8
168	Novartis Investigative Site	Daugavpils		Latvia	LV-5401
169	Novartis Investigative Site	Daugavpils		Latvia	LV-5417
170	Novartis Investigative Site	Riga		Latvia	LV 1002
171	Novartis Investigative Site	Kaunas	LTU	Lithuania	LT 50161
172	Novartis Investigative Site	Klaipeda	LTU	Lithuania	LT-93220
173	Novartis Investigative Site	Vilnius	LTU	Lithuania	LT-05263
174	Novartis Investigative Site	Vilnius	LTU	Lithuania	LT-08406
175	Novartis Investigative Site	Vilnius	LTU	Lithuania	LT-10207
176	Novartis Investigative Site	Kaunas	LT	Lithuania	LT-50128
177	Novartis Investigative Site	Kaunas		Lithuania	LT-45130
178	Novartis Investigative Site	Klaipeda		Lithuania	LT-92231
179	Novartis Investigative Site	Bulacan		Philippines	3020
180	Novartis Investigative Site	Manila		Philippines	1000
181	Novartis Investigative Site	Quezon City		Philippines	1100
182	Novartis Investigative Site	Kielce	POL	Poland	25-371
183	Novartis Investigative Site	Bialystok		Poland	15 276
184	Novartis Investigative Site	Bialystok		Poland	15-010
185	Novartis Investigative Site	Biaystok		Poland	15-430
186	Novartis Investigative Site	Poznan		Poland	60-214
187	Novartis Investigative Site	Poznan		Poland	60-693
188	Novartis Investigative Site	Poznan		Poland	60-823
189	Novartis Investigative Site	Strzelce Opolskie		Poland	47 100
190	Novartis Investigative Site	Ploiesti	Prahova	Romania	100024
191	Novartis Investigative Site	Constanta	ROM	Romania	900412
192	Novartis Investigative Site	Timisoara	Timis	Romania	300310
193	Novartis Investigative Site	Arad		Romania	310013
194	Novartis Investigative Site	Bragadiru		Romania	077025
195	Novartis Investigative Site	Brasov		Romania	500051
196	Novartis Investigative Site	Brasov		Romania	500086
197	Novartis Investigative Site	Brasov		Romania	500283
198	Novartis Investigative Site	Brasov		Romania	500366
199	Novartis Investigative Site	Bucharest		Romania	030317
200	Novartis Investigative Site	Bucuresti		Romania	050554
201	Novartis Investigative Site	Cluj Napoca		Romania	400139
202	Novartis Investigative Site	Cluj Napoca		Romania	400371
203	Novartis Investigative Site	Deva		Romania	330162
204	Novartis Investigative Site	Oradea		Romania	410176
205	Novartis Investigative Site	Sangiorgiu De Mures		Romania	547530
206	Novartis Investigative Site	Singapore	SGP	Singapore	117599
207	Novartis Investigative Site	Singapore		Singapore	169608
208	Novartis Investigative Site	Singapore		Singapore	529889
209	Novartis Investigative Site	Barcelona		Spain	08006
210	Novartis Investigative Site	Basel		Switzerland	4031
211	Novartis Investigative Site	Liestal		Switzerland	4410
212	Novartis Investigative Site	Lugano		Switzerland	6900
213	Novartis Investigative Site	St Gallen		Switzerland	9007
214	Novartis Investigative Site	Zurich		Switzerland	8032
215	Novartis Investigative Site	Cambridge	Cambrigdeshire	United Kingdom	CB2 0QQ
216	Novartis Investigative Site	Darlington	Durham	United Kingdom	DL3 6HX
217	Novartis Investigative Site	London	GBR	United Kingdom	EC1M 6BQ
218	Novartis Investigative Site	Sheffield	South Yorkshire	United Kingdom	S10 2JF
219	Novartis Investigative Site	Bradford	West Yorkshire	United Kingdom	BD9 6RJ
220	Novartis Investigative Site	Birmingham		United Kingdom	B15 2WB
221	Novartis Investigative Site	Birmingham		United Kingdom	B9 5SS
222	Novartis Investigative Site	Cardiff		United Kingdom	CF14 4XW
223	Novartis Investigative Site	Chertsey		United Kingdom	KT16 0PZ
224	Novartis Investigative Site	East Yorkshire		United Kingdom	HU16 5JQ
225	Novartis Investigative Site	Leicester		United Kingdom	LE3 9QP
226	Novartis Investigative Site	Nottingham		United Kingdom	NG5 1PB
227	Novartis Investigative Site	Plymouth		United Kingdom	PL6 8DH
228	Novartis Investigative Site	Tyne And Wear		United Kingdom	NE29 8NH
229	Novartis Investigative Site	Wakefield		United Kingdom	WF1 4DG
230	Novartis Investigative Site	Wishaw		United Kingdom	ML2 0DP
231	Novartis Investigative Site	Ho Chi Minh	VNM	Vietnam	700000
232	Novartis Investigative Site	Hanoi		Vietnam	100000
233	Novartis Investigative Site	Ho Chi Minh		Vietnam	700000

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 29, 2019
• Study Protocol - Feb 10, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02555683
• Other Study ID Numbers: CQAW039A2307; 2015-002553-35
• First Posted: Sep 21, 2015
• Last Update Posted: May 18, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Asthma; QAW039; allergic asthma; allergy triggered asthma; reactive asthma; asthma attack; difficulty breathing
• Additional relevant MeSH terms: Asthma; Indoleacetic Acids

Study Results

Participant Flow

Recruitment Details	Participants were from Argentina, Australia, Austria, Belgium, Brazil, China, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Hungary, Latvia, Lithuania, Philippines, Poland, Romania, Singapore, Spain, Switzerland, UK, US, Vietnam.
Pre-assignment Detail	The study included a Screening period of up to 2 weeks and a Placebo Run-in period of 2 to 6 weeks, during which eligibility for randomization was determined.

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Period Title: Overall Study
STARTED	301	295	298
FAS/SAF: High Eosinophil Subpopulation	200	201	201
FAS/SAF: Overall Population	299	293	298
COMPLETED	282	278	269
NOT COMPLETED	19	17	29

Baseline Characteristics

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo	Total
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily	Total of all reporting groups
Overall Participants	301	295	298	894
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.9 (14.97)	51.1 (14.29)	50.3 (14.48)	50.4 (14.58)
Sex: Female, Male (Count of Participants)
Female	192 63.8%	214 72.5%	177 59.4%	583 65.2%
Male	109 36.2%	81 27.5%	121 40.6%	311 34.8%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	214 71.1%	215 72.9%	213 71.5%	642 71.8%
Black	11 3.7%	6 2%	12 4%	29 3.2%
Asian	45 15%	38 12.9%	44 14.8%	127 14.2%
Native American	24 8%	29 9.8%	24 8.1%	77 8.6%
Unknown	1 0.3%	2 0.7%	3 1%	6 0.7%
Other	6 2%	5 1.7%	2 0.7%	13 1.5%

Outcome Measures

1. Primary Outcome

Title	Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in High Eosinophils Subpopulation
Description	A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in high eosinophils subpopulation (count ≥ 250 cells/μL)

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	200	201	201
Least Squares Mean (95% Confidence Interval) [events/year]	0.97	0.77	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.800
	Comments	adjusted p-value
	Method	negative binomial regression model
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	rate ratio
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.510
	Comments	adjusted p-value
	Method	negative binomial regression model
	Comments	Adjusted p-values are based on the closed testing procedure
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in High Eosinophils Subpopulation
Description	The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in high eosinophils subpopulation (count ≥ 250 cells/μL)

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	200	201	201
Least Squares Mean (Standard Error) [units on scale]	0.75 (0.067)	0.81 (0.067)	0.68 (0.067)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.095
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments	adjusted p-vale
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.095
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in High Eosinophils Subpopulation
Description	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled). The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in high eosinophils subpopulation (count ≥ 250 cells/μL)

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	200	201	201
Least Squares Mean (Standard Error) [units on scale]	-0.88 (0.069)	-0.94 (0.069)	-0.76 (0.070)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.098
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.098
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in High Eosinophils Subpopulation
Description	Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. The high eosinophils subpopulation consists of all patients with blood eosinophil count ≥ 250 cells/μL at baseline.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in high eosinophils subpopulation (count ≥ 250 cells/μL)

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	200	201	201
Least Squares Mean (Standard Error) [Liter]	0.169 (0.0257)	0.153 (0.0255)	0.103 (0.0260)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.800
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.067
	Confidence Interval	(2-Sided) 95%; -0.005 to 0.139
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0365
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.523
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.050
	Confidence Interval	(2-Sided) 95%; -0.021 to 0.121
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0363
	Estimation Comments

5. Primary Outcome

Title	Rate of Moderate-to-severe Asthma Exacerbations During the 52-week Treatment Period in Overall Population
Description	A severe asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and hospitalization; or treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days and emergency department visit (greater than 24 hours*); or death due to asthma. A moderate asthma exacerbation is defined as treatment with 'rescue' systemic corticosteroids for greater than or equal to 3 days either as an outpatient or in emergency department visits (Emergency department visit less than or equal to 24 hours).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in overall population

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	299	293	298
Least Squares Mean (95% Confidence Interval) [events/year]	0.92	0.75	0.96

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	negative binomial regression model
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	rate ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.510
	Comments	adjusted p-value
	Method	negative binomial regression model
	Comments	Adjusted p-values are based on the closed testing procedure
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score in Overall Population
Description	The AQLQ+12 is comprised of a total of 32 individual questions that span a total of four domains: symptoms, activity limitation, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale (7 = not at all impaired to 1 = severely impaired). The AQLQ+12 yields individual domain scores, which is the mean of all items in each domain, and an overall score, which is the mean of all 32 individual responses. Higher scores indicate less impairment in health-related quality of life.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in overall population

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	299	293	298
Least Squares Mean (Standard Error) [units on scale]	0.68 (0.053)	0.73 (0.054)	0.61 (0.054)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.076
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments	adjusted p-vale
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.076
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline to Week 52 in Asthma Control Questionnaire-5(ACQ-5) Score in Overall Population
Description	The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. Patients were asked to recall how their asthma had been during the previous week and to respond to the symptom questions on a 7-point scale (0=no impairment, 6=maximum impairment). The questions are equally weighted and the ACQ-5 score is the mean of the 5 questions: therefore, between 0 (totally controlled) and 6 (severely uncontrolled).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) overall population

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	299	293	298
Least Squares Mean (Standard Error) [units on scale]	-0.83 (0.055)	-0.90 (0.056)	-0.71 (0.056)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.079
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.35 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.079
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline to Week 52 in Pre-dose Forced Expiratory Volume in 1 Second (FEV1) in Overall Population
Description	Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) in overall population

Arm/Group Title	QAW039 150 mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 150 mg once daily	QAW039 450 mg once daily	Placebo once daily
Measure Participants	299	293	298
Least Squares Mean (Standard Error) [Liter]	0.144 (0.0205)	0.108 (0.0206)	0.068 (0.0209)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.076
	Confidence Interval	(2-Sided) 95%; 0.019 to 0.134
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0292
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.591
	Comments	adjusted p-value
	Method	ANCOVA
	Comments	Adjusted p-values obtained from the closed testing procedure
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.040
	Confidence Interval	(2-Sided) 95%; -0.017 to 0.097
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0292
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 7 days post treatment. Serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 56 weeks.
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment plus 7 days post treatment for adverse events and 30 days post treatment for serious adverse events.
Arm/Group Title	QAW039 150 mg		QAW039 450 mg		Placebo
Arm/Group Description	QAW039 150 mg		QAW039 450 mg		Placebo
All Cause Mortality
	QAW039 150 mg		QAW039 450 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/299 (0%)		1/293 (0.3%)		2/298 (0.7%)
Serious Adverse Events
	QAW039 150 mg		QAW039 450 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/299 (11%)		30/293 (10.2%)		32/298 (10.7%)
Blood and lymphatic system disorders
Lymphadenopathy	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Cardiac disorders
Acute coronary syndrome	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Acute myocardial infarction	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Atrial tachycardia	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Cardio-respiratory arrest	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Coronary artery disease	1/299 (0.3%)		0/293 (0%)		1/298 (0.3%)
Myocardial infarction	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Myocardial ischaemia	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Pericardial effusion	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Sinus tachycardia	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Ventricular hypokinesia	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Gastrointestinal disorders
Diaphragmatic hernia	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Diverticulum intestinal	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Faecaloma	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Gastritis	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Hiatus hernia	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Intestinal obstruction	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Irritable bowel syndrome	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Large intestine polyp	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Megacolon	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Oesophageal food impaction	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Pancreatitis acute	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Umbilical hernia	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
General disorders
Non-cardiac chest pain	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Pyrexia	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Hepatobiliary disorders
Biliary colic	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Immune system disorders
Drug hypersensitivity	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Infections and infestations
Appendicitis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Bacterial diarrhoea	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Chronic hepatitis C	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Cystitis	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Diverticulitis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Gastroenteritis	1/299 (0.3%)		0/293 (0%)		1/298 (0.3%)
Herpes virus infection	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Influenza	1/299 (0.3%)		2/293 (0.7%)		1/298 (0.3%)
Pneumonia	3/299 (1%)		5/293 (1.7%)		1/298 (0.3%)
Pneumonia chlamydial	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Rectal abscess	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Tracheobronchitis	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Upper respiratory tract infection bacterial	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Viral upper respiratory tract infection	2/299 (0.7%)		0/293 (0%)		0/298 (0%)
Injury, poisoning and procedural complications
Abdominal wound dehiscence	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Ankle fracture	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Femur fracture	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Incisional hernia	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Radius fracture	2/299 (0.7%)		0/293 (0%)		0/298 (0%)
Tendon rupture	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Traumatic haematoma	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Ulna fracture	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Wrist fracture	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Investigations
Electrocardiogram abnormal	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Metabolism and nutrition disorders
Dehydration	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Hypoalbuminaemia	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Type 2 diabetes mellitus	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Spinal osteoarthritis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Tenosynovitis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Thoracic spinal stenosis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Epithelioid mesothelioma	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Leiomyosarcoma	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Non-small cell lung cancer	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Rectal cancer	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Squamous cell carcinoma	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Testicular neoplasm	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Uterine leiomyoma	1/299 (0.3%)		0/293 (0%)		1/298 (0.3%)
Nervous system disorders
Cerebrovascular accident	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Essential tremor	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Headache	1/299 (0.3%)		0/293 (0%)		1/298 (0.3%)
Ischaemic stroke	1/299 (0.3%)		1/293 (0.3%)		0/298 (0%)
Lumbar radiculopathy	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Migraine	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Superior sagittal sinus thrombosis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Transient ischaemic attack	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Psychiatric disorders
Completed suicide	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Depression	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Renal and urinary disorders
Acute kidney injury	1/299 (0.3%)		2/293 (0.7%)		0/298 (0%)
Glomerulonephritis	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Glomerulonephritis chronic	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Nephrolithiasis	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Renal colic	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Reproductive system and breast disorders
Adnexa uteri cyst	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Benign prostatic hyperplasia	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Ovarian cyst	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	10/299 (3.3%)		8/293 (2.7%)		14/298 (4.7%)
Dyspnoea	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Nasal polyps	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Pulmonary embolism	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Pulmonary oedema	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Respiratory failure	0/299 (0%)		1/293 (0.3%)		0/298 (0%)
Vascular disorders
Aortic aneurysm	0/299 (0%)		0/293 (0%)		1/298 (0.3%)
Hypertension	1/299 (0.3%)		0/293 (0%)		0/298 (0%)
Other (Not Including Serious) Adverse Events
	QAW039 150 mg		QAW039 450 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	204/299 (68.2%)		193/293 (65.9%)		214/298 (71.8%)
Infections and infestations
Bronchitis	29/299 (9.7%)		22/293 (7.5%)		26/298 (8.7%)
Lower respiratory tract infection	12/299 (4%)		10/293 (3.4%)		7/298 (2.3%)
Nasopharyngitis	43/299 (14.4%)		37/293 (12.6%)		49/298 (16.4%)
Rhinitis	8/299 (2.7%)		11/293 (3.8%)		12/298 (4%)
Sinusitis	18/299 (6%)		19/293 (6.5%)		18/298 (6%)
Upper respiratory tract infection	35/299 (11.7%)		35/293 (11.9%)		31/298 (10.4%)
Upper respiratory tract infection bacterial	13/299 (4.3%)		14/293 (4.8%)		21/298 (7%)
Urinary tract infection	11/299 (3.7%)		15/293 (5.1%)		18/298 (6%)
Viral upper respiratory tract infection	29/299 (9.7%)		26/293 (8.9%)		26/298 (8.7%)
Investigations
Blood creatinine increased	13/299 (4.3%)		11/293 (3.8%)		9/298 (3%)
Musculoskeletal and connective tissue disorders
Back pain	16/299 (5.4%)		16/293 (5.5%)		11/298 (3.7%)
Nervous system disorders
Headache	28/299 (9.4%)		22/293 (7.5%)		24/298 (8.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	151/299 (50.5%)		135/293 (46.1%)		155/298 (52%)
Cough	11/299 (3.7%)		5/293 (1.7%)		13/298 (4.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.