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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03052517
• Collaborator: (none)
• Enrollment: 2,538
• Locations: 348
• Arms: 3
• Actual Duration (Months): 35.8
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study was a 2-treatment period, randomized, multicenter parallel-group study. The overall purpose of this study was to provide long- term safety data for fevipiprant (QAW039) (Dose 1 and Dose 2), compared with placebo, when added to the Global Initiative for Asthma (GINA) steps 3, 4, and 5 standard-of-care (SoC) asthma therapy (GINA 2016), in patients with moderate-to- severe asthma.

The purpose of this study was to provide long-term safety data for QAW039 150 mg once daily and 450 mg once daily, compared with placebo, when added to GINA steps 3, 4, and 5 standard-of-care asthma therapy (GINA 2020) in adult and adolescent (≥12 years) patients with moderate-to-severe asthma. The study included 2 cohorts of patients:

1. Rollover patients who had completed any of the four Phase 3 pivotal efficacy studies with QAW039 (QAW039A2307, QAW039A2314, QAW039A2316, or QAW039A2317, hereafter referred to as Studies A2307, A2314, A2316, and A2317), thus providing data for a longer duration of exposure, and

2. New patients who had not previously participated in a study of QAW039, permitting an increase in the number of patients with long-term exposure to QAW039.

By including these 2 categories of patients, the total number of patients treated with QAW039 as well as the duration of exposure to QAW039 treatment was substantially increased, supporting evaluation of the safety profile of QAW039.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QAW039 150 mg; Drug: QAW039 450 mg; Drug: Placebo	Phase 3

Detailed Description

The study comprised 2-treatment period. Treatment Period 1 was a 52-week, double-blind treatment period in which QAW039 450 mg or 150 mg or placebo was added to standard-of-care asthma therapy according to GINA guidelines. Treatment Period 2 was an optional 104-week, single-blind treatment period in which patients received QAW039 450 mg or 150 mg or placebo added to standard-of-care asthma therapy according to GINA guidelines.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2538 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 2-treatment Period, Randomized, Placebo-controlled, Multicenter Parallel-group Study to Assess the Safety of QAW039 When Added to Existing Asthma Therapy in GINA Steps 3, 4 and 5 Patients With Uncontrolled Asthma.
• Actual Study Start Date: Mar 21, 2017
• Actual Primary Completion Date: Feb 19, 2020
• Actual Study Completion Date: Mar 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QAW039 150mg QAW039 Dose 1 once daily	Drug: QAW039 150 mg; One tablet of QAW039 150 mg once daily
Experimental: QAW039 450 mg QAW039 Dose 2 once daily	Drug: QAW039 450 mg; One tablet of QAW039 450 mg once daily
Placebo Comparator: Placebo Placebo once daily	Drug: Placebo; One tablet of Placebo once daily

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 52 - Cox Regression Model [52 weeks]

   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.

2. Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 156 - Cox Regression Model [156 weeks]

   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

3. Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 52 - Cox Regression Model [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.

4. Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 156 - Cox Regression Model [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.

5. Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 52 - Cox Regression Model [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.

6. Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 156 - Cox Regression Model [156 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

Secondary Outcome Measures

1. Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model [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)

2. Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model [156 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)

3. Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 52 [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.

4. Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 156 [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.

5. Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 52 [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

6. Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 156 [156 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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients completing a prior Phase 3 study of QAW039:

• Informed consent and assent (if applicable).

• Completion of the Treatment Period (on blinded study drug) of a prior Phase 3 study of QAW039.

• Patient is able to safely continue into the study as judged by the investigator.

Patients who have not previously participated in a study of QAW039:

• Written informed consent.

• A diagnosis of asthma,uncontrolled on GINA 3/4/5 asthma medication.

• Evidence of airway reversibility or airway hyper- reactivity.

• FEV1 of ≤85% of the predicted normal value.

• An ACQ score ≥1.5 prior to entering the study.

Exclusion Criteria:

Patients completing a prior phase 3 study of QAW039:

• Pregnant or nursing (lactating) women.

• Women of child-bearing potential unless they are using basic methods of contraception during dosing of study drug

• Patients who did not complete the Treatment Period on blinded study drug of the prior QAW039 study they participated in.

• Inability to comply with all study requirements.

• Patient who experienced a serious and drug-related AE in the prior QAW039 study they participated in.

Patients who have not previously participated in a study of QAW039:

• 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 (i.e.-the patient was randomized in another study).

• 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> 40 mg of atorvastatin, >40 mg of pravastatin, or >2 mg of pitavastatin. Statin doses less than or equal to these doses as well as other statins will be permitted during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35209
2	Novartis Investigative Site	Encinitas	California	United States	92024
3	Novartis Investigative Site	Newport Beach	California	United States	92663
4	Novartis Investigative Site	Orange	California	United States	92868
5	Novartis Investigative Site	San Diego	California	United States	92117
6	Novartis Investigative Site	Stockton	California	United States	95207
7	Novartis Investigative Site	Walnut Creek	California	United States	94598
8	Novartis Investigative Site	Westminster	California	United States	92683
9	Novartis Investigative Site	Colorado Springs	Colorado	United States	80907
10	Novartis Investigative Site	Denver	Colorado	United States	80230
11	Novartis Investigative Site	Lafayette	Colorado	United States	80026
12	Novartis Investigative Site	Miami	Florida	United States	33176
13	Novartis Investigative Site	Tamarac	Florida	United States	33321
14	Novartis Investigative Site	Winter Park	Florida	United States	32789
15	Novartis Investigative Site	Marietta	Georgia	United States	30060
16	Novartis Investigative Site	Overland Park	Kansas	United States	66210
17	Novartis Investigative Site	Louisville	Kentucky	United States	40215
18	Novartis Investigative Site	Zachary	Louisiana	United States	70791
19	Novartis Investigative Site	Bangor	Maine	United States	04401
20	Novartis Investigative Site	Columbia	Maryland	United States	21044
21	Novartis Investigative Site	Waldorf	Maryland	United States	20602
22	Novartis Investigative Site	Ypsilanti	Michigan	United States	48197
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24	Novartis Investigative Site	Bellevue	Nebraska	United States	68123
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35	Novartis Investigative Site	Altoona	Pennsylvania	United States	16602
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37	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15241
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47	Novartis Investigative Site	Berazategui	Buenos Aires	Argentina	1888
48	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1056ABJ
49	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
50	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425BEN
51	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1426ABP
52	Novartis Investigative Site	Lanus	Buenos Aires	Argentina	B8000XAV
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55	Novartis Investigative Site	Santa Rosa	La Pampa	Argentina	6300
56	Novartis Investigative Site	Santa Fe	Rosario	Argentina	S2000DBS
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101	Novartis Investigative Site	Montreal	Quebec	Canada	H3G 1L5
102	Novartis Investigative Site	Montreal	Quebec	Canada	H3T 1E2
103	Novartis Investigative Site	Montreal	Quebec	Canada	H4J 1C5
104	Novartis Investigative Site	Quebec		Canada	G1V 4W2
105	Novartis Investigative Site	Vancouver		Canada
106	Novartis Investigative Site	Guang Zhou	Guang Dong Province	China	510120
107	Novartis Investigative Site	Shijiazhuang	Hebei	China	050000
108	Novartis Investigative Site	Nanjing	Jiangsu	China	210006
109	Novartis Investigative Site	Nanjing	Jiangsu	China	210009
110	Novartis Investigative Site	Chang Chun	Jilin	China	130021
111	Novartis Investigative Site	Shenyang	Liaoning	China	110000
112	Novartis Investigative Site	Shenyang	Liaoning	China	110003
113	Novartis Investigative Site	Xian	Shanxi	China	710061
114	Novartis Investigative Site	Chengdu	Sichuan	China	610041
115	Novartis Investigative Site	Beijing		China	100050
116	Novartis Investigative Site	Chongqing		China	400037
117	Novartis Investigative Site	Shanghai		China	200433
118	Novartis Investigative Site	Ibague	Tolima	Colombia	730006
119	Novartis Investigative Site	Bogota		Colombia	110221
120	Novartis Investigative Site	Bucaramanga		Colombia
121	Novartis Investigative Site	Jindrichuv Hradec	Czech Republic	Czechia	377 01
122	Novartis Investigative Site	Teplice	Czech Republic	Czechia	415 01
123	Novartis Investigative Site	Teplice	CZE	Czechia	415 01
124	Novartis Investigative Site	Brno		Czechia	615 00
125	Novartis Investigative Site	Karlovy Vary		Czechia	360 17
126	Novartis Investigative Site	Mlada Boleslav		Czechia	293 50
127	Novartis Investigative Site	Tallinn		Estonia	13419
128	Novartis Investigative Site	Tartu		Estonia	51014
129	Novartis Investigative Site	Helsinki		Finland	00029
130	Novartis Investigative Site	Montpellier cedex 5	Herault	France	34059
131	Novartis Investigative Site	Dijon		France	21000
132	Novartis Investigative Site	Le Kremlin Bicetre		France	94275
133	Novartis Investigative Site	Lyon Cedex 04		France	69317
134	Novartis Investigative Site	Marseille		France	13015
135	Novartis Investigative Site	Nantes		France	44093
136	Novartis Investigative Site	Paris cedex 18		France	75877
137	Novartis Investigative Site	Strasbourg Cedex		France	67091
138	Novartis Investigative Site	Cottbus	Sachsen	Germany	03050
139	Novartis Investigative Site	Aschaffenburg		Germany	63739
140	Novartis Investigative Site	Berlin		Germany	10717
141	Novartis Investigative Site	Berlin		Germany	10969
142	Novartis Investigative Site	Berlin		Germany	12159
143	Novartis Investigative Site	Berlin		Germany	12203
144	Novartis Investigative Site	Frankfurt		Germany	60389
145	Novartis Investigative Site	Frankfurt		Germany	60596
146	Novartis Investigative Site	Landsberg		Germany	86899
147	Novartis Investigative Site	Leipzig		Germany	04357
148	Novartis Investigative Site	Witten		Germany	58452
149	Novartis Investigative Site	Athens	GR	Greece	115 25
150	Novartis Investigative Site	Athens	GR	Greece	115 27
151	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
152	Novartis Investigative Site	Athens		Greece	115 21
153	Novartis Investigative Site	Athens		Greece	115 27
154	Novartis Investigative Site	Athens		Greece	175 62
155	Novartis Investigative Site	Gautemala City	Gautemala	Guatemala	01010
156	Novartis Investigative Site	Guatemala City	GTM	Guatemala	01010
157	Novartis Investigative Site	Guatemala City	GTM	Guatemala	01011
158	Novartis Investigative Site	Guatemala City		Guatemala	01010
159	Novartis Investigative Site	Guatemala City		Guatemala	01011
160	Novartis Investigative Site	Budaors	HUN	Hungary	2040
161	Novartis Investigative Site	Gyor	HUN	Hungary	9024
162	Novartis Investigative Site	Hajdunanas	HUN	Hungary	4080
163	Novartis Investigative Site	Puspokladany	HUN	Hungary	4150
164	Novartis Investigative Site	Szazhalombatta	HUN	Hungary	2440
165	Novartis Investigative Site	Budapest		Hungary	1106
166	Novartis Investigative Site	Godollo		Hungary	2100
167	Novartis Investigative Site	Komarom		Hungary	2900
168	Novartis Investigative Site	Mako		Hungary	6900
169	Novartis Investigative Site	Pecs		Hungary	7635
170	Novartis Investigative Site	Siofok		Hungary	8600
171	Novartis Investigative Site	Szeged		Hungary	6722
172	Novartis Investigative Site	Torokbalint		Hungary	2045
173	Novartis Investigative Site	Ahmedabad	Gujarat	India	380 060
174	Novartis Investigative Site	Vadodara	Gujarat	India	390022
175	Novartis Investigative Site	Nagpur	Maharashtra	India	440015
176	Novartis Investigative Site	Pune	Maharashtra	India	411014
177	Novartis Investigative Site	Bikaner	Rajasthan	India	334 001
178	Novartis Investigative Site	Jaipur	Rajasthan	India	302039
179	Novartis Investigative Site	Coimbatore	Tamil Nadu	India	641 045
180	Novartis Investigative Site	DehraDun	Uttarakhand	India	248001
181	Novartis Investigative Site	Ashkelon		Israel	78278
182	Novartis Investigative Site	Haifa		Israel	310 9601
183	Novartis Investigative Site	Haifa		Israel	3436212
184	Novartis Investigative Site	Jerusalem		Israel	91031
185	Novartis Investigative Site	Jerusalem		Israel	91120
186	Novartis Investigative Site	Petach Tikva		Israel	49100
187	Novartis Investigative Site	Rehovot		Israel	76100
188	Novartis Investigative Site	Nagoya	Aichi	Japan	466 8560
189	Novartis Investigative Site	Matsuyama-city	Ehime	Japan	790-0024
190	Novartis Investigative Site	Matsuyama-city	Ehime	Japan	790-8524
191	Novartis Investigative Site	Chikushino-city	Fukuoka	Japan	818-8502
192	Novartis Investigative Site	Fukuoka city	Fukuoka	Japan	811-1394
193	Novartis Investigative Site	Iizuka-city	Fukuoka	Japan	820-8505
194	Novartis Investigative Site	Kasuga-city	Fukuoka	Japan	816-0813
195	Novartis Investigative Site	Koga city	Fukuoka	Japan	811 3195
196	Novartis Investigative Site	Yanagawa-city	Fukuoka	Japan	832-0059
197	Novartis Investigative Site	Mizunami-city	Gifu	Japan	509 6134
198	Novartis Investigative Site	Hiroshima-city	Hiroshima	Japan	734-8530
199	Novartis Investigative Site	Sapporo	Hokkaido	Japan	062-0931
200	Novartis Investigative Site	Sapporo	Hokkaido	Japan	064-0804
201	Novartis Investigative Site	Himeji-city	Hyogo	Japan	672-8064
202	Novartis Investigative Site	Naka-gun	Ibaraki	Japan	319-1113
203	Novartis Investigative Site	Sakaide	Kagawa	Japan	762-8550
204	Novartis Investigative Site	Takamatsu-city	Kagawa	Japan	761-8073
205	Novartis Investigative Site	Kagoshima city	Kagoshima	Japan	890 8520
206	Novartis Investigative Site	Sagamihara-city	Kanagawa	Japan	228-8522
207	Novartis Investigative Site	Sagamihara-city	Kanagawa	Japan	229-1103
208	Novartis Investigative Site	Yokohama city	Kanagawa	Japan	232 0024
209	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	223-0059
210	Novartis Investigative Site	Yokohama	Kanagawa	Japan	234-0054
211	Novartis Investigative Site	Koshi-city	Kumamoto	Japan	861-1196
212	Novartis Investigative Site	Matsusaka-city	Mie	Japan	515-8544
213	Novartis Investigative Site	Tsu-city	Mie	Japan	514-0125
214	Novartis Investigative Site	Sendai-city	Miyagi	Japan	980-0871
215	Novartis Investigative Site	Sendai-city	Miyagi	Japan	984-8560
216	Novartis Investigative Site	Kashihara city	Nara	Japan	634 8522
217	Novartis Investigative Site	Habikino city	Osaka	Japan	583 8588
218	Novartis Investigative Site	Kishiwada-city	Osaka	Japan	596-8501
219	Novartis Investigative Site	Tokyo	Shibuya Ku	Japan	150 0013
220	Novartis Investigative Site	Hamamatsu-city	Shizuoka	Japan	431-3192
221	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104-0031
222	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104-8560
223	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0003
224	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0028
225	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
226	Novartis Investigative Site	Kiyose-city	Tokyo	Japan	204-8585
227	Novartis Investigative Site	Ota-ku	Tokyo	Japan	145 0063
228	Novartis Investigative Site	Setagaya-Ku	Tokyo	Japan	157-0072
229	Novartis Investigative Site	Setagaya-ku	Tokyo	Japan	157006
230	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	142-8666
231	Novartis Investigative Site	Shinjuku ku	Tokyo	Japan	162 8655
232	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	169-0073
233	Novartis Investigative Site	Toshima ku	Tokyo	Japan	170 0003
234	Novartis Investigative Site	Daugavpils		Latvia	LV-5401
235	Novartis Investigative Site	Riga		Latvia	LV 1002
236	Novartis Investigative Site	El Chouf	LBN	Lebanon	1503201002
237	Novartis Investigative Site	Ashrafieh		Lebanon	166830
238	Novartis Investigative Site	Beirut		Lebanon	166378
239	Novartis Investigative Site	Kaunas	LTU	Lithuania	LT 50161
240	Novartis Investigative Site	Vilnius	LTU	Lithuania	LT-10207
241	Novartis Investigative Site	Kaunas	LT	Lithuania	LT-45130
242	Novartis Investigative Site	Kaunas	LT	Lithuania	LT-50128
243	Novartis Investigative Site	Klaipeda		Lithuania	LT-92231
244	Novartis Investigative Site	Vilnius		Lithuania	LT-04129
245	Novartis Investigative Site	Kota Bharu	Kelantan	Malaysia	15586
246	Novartis Investigative Site	Kuantan	Pahang	Malaysia	25100
247	Novartis Investigative Site	Taiping	Perak	Malaysia	34000
248	Novartis Investigative Site	Guadalajara Jalisco	Jalisco	Mexico	44220
249	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44130
250	Novartis Investigative Site	Rio De Janeiro		Mexico	06700
251	Novartis Investigative Site	Arnhem		Netherlands	6815 AD
252	Novartis Investigative Site	Leeuwarden		Netherlands	8934 AD
253	Novartis Investigative Site	Cercado De Lima	Lima	Peru	01
254	Novartis Investigative Site	San Isidro	Lima	Peru	27
255	Novartis Investigative Site	San Martin de Porres	Lima	Peru	31
256	Novartis Investigative Site	Cusco		Peru	84
257	Novartis Investigative Site	Lima		Peru	1
258	Novartis Investigative Site	Piura		Peru	2000
259	Novartis Investigative Site	Lipa City	Batangas	Philippines	4217
260	Novartis Investigative Site	Quezon City	Manila	Philippines	1100
261	Novartis Investigative Site	Bulacan		Philippines	3020
262	Novartis Investigative Site	Iloilo City		Philippines	5000
263	Novartis Investigative Site	Manila		Philippines	1000
264	Novartis Investigative Site	Quezon City		Philippines	1100
265	Novartis Investigative Site	Bialystok		Poland	15-010
266	Novartis Investigative Site	Kielce		Poland	25-371
267	Novartis Investigative Site	Poznan		Poland	60-214
268	Novartis Investigative Site	Poznan		Poland	60-693
269	Novartis Investigative Site	Poznan		Poland	60-823
270	Novartis Investigative Site	Strzelce Opolskie		Poland	47 100
271	Novartis Investigative Site	San Juan		Puerto Rico	00909
272	Novartis Investigative Site	Bucharest	District 3	Romania	030303
273	Novartis Investigative Site	Constanta	ROM	Romania	900412
274	Novartis Investigative Site	Timisoara	Timis	Romania	300310
275	Novartis Investigative Site	Bragadiru		Romania	077025
276	Novartis Investigative Site	Brasov		Romania	500051
277	Novartis Investigative Site	Brasov		Romania	500086
278	Novartis Investigative Site	Brasov		Romania	500283
279	Novartis Investigative Site	Brasov		Romania	500366
280	Novartis Investigative Site	Cluj Napoca		Romania	400139
281	Novartis Investigative Site	Cluj-Napoca		Romania	400371
282	Novartis Investigative Site	Deva		Romania	330162
283	Novartis Investigative Site	Barnaul		Russian Federation	656024
284	Novartis Investigative Site	Chelyabinsk		Russian Federation	454021
285	Novartis Investigative Site	Izhevsk		Russian Federation	426061
286	Novartis Investigative Site	Moscow		Russian Federation	115478
287	Novartis Investigative Site	Moscow		Russian Federation	125315
288	Novartis Investigative Site	Nizhnii Novgorod		Russian Federation	603126
289	Novartis Investigative Site	Penza		Russian Federation	440067
290	Novartis Investigative Site	Perm		Russian Federation	614068
291	Novartis Investigative Site	Ryazan		Russian Federation	390039
292	Novartis Investigative Site	Saint Petersburg		Russian Federation	194354
293	Novartis Investigative Site	Saint-Petersburg		Russian Federation	191186
294	Novartis Investigative Site	Sestroretsk		Russian Federation	197706
295	Novartis Investigative Site	Smolensk		Russian Federation
296	Novartis Investigative Site	St Petersburg		Russian Federation	194354
297	Novartis Investigative Site	Stavropol		Russian Federation	355000
298	Novartis Investigative Site	Yaroslavl		Russian Federation	150054
299	Novartis Investigative Site	Yekaterinburg		Russian Federation	620109
300	Novartis Investigative Site	Jeddah		Saudi Arabia	21423
301	Novartis Investigative Site	Belgrade		Serbia	11000
302	Novartis Investigative Site	Belgrade		Serbia	11070
303	Novartis Investigative Site	Kragujevac		Serbia	34000
304	Novartis Investigative Site	Nis		Serbia	18000
305	Novartis Investigative Site	Sremska Kamenica		Serbia	21204
306	Novartis Investigative Site	Singapore		Singapore	119228
307	Novartis Investigative Site	Singapore		Singapore	529889
308	Novartis Investigative Site	Bardejov	Slovak Republic	Slovakia	085 01
309	Novartis Investigative Site	Bojnice	Slovak Republic	Slovakia	972 01
310	Novartis Investigative Site	Kezmarok		Slovakia	060 01
311	Novartis Investigative Site	Komarno		Slovakia	945 01
312	Novartis Investigative Site	Kosice		Slovakia	040 01
313	Novartis Investigative Site	Levice		Slovakia	934 01
314	Novartis Investigative Site	Levice		Slovakia	93401
315	Novartis Investigative Site	Poprad		Slovakia	058 01
316	Novartis Investigative Site	Presov		Slovakia	080 01
317	Novartis Investigative Site	Spisska Nova Ves		Slovakia	052 01
318	Novartis Investigative Site	Zilina		Slovakia	01207
319	Novartis Investigative Site	Malaga	Andalucia	Spain	29009
320	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
321	Novartis Investigative Site	Marbella	Andalucia	Spain	29603
322	Novartis Investigative Site	Jerez	Cadiz	Spain	11407
323	Novartis Investigative Site	Laredo	Cantabria	Spain	39770
324	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
325	Novartis Investigative Site	Lugo	Galicia	Spain	27003
326	Novartis Investigative Site	Palma de Mallorca	Islas Baleares	Spain	07010
327	Novartis Investigative Site	Barcelona	Vic	Spain	08500
328	Novartis Investigative Site	Barcelona		Spain	08006
329	Novartis Investigative Site	Girona		Spain	17005
330	Novartis Investigative Site	Guadalajara		Spain	19002
331	Novartis Investigative Site	Madrid		Spain	28046
332	Novartis Investigative Site	Santiago de Compostela		Spain	15706
333	Novartis Investigative Site	Zaragoza		Spain	50009
334	Novartis Investigative Site	Liestal		Switzerland	4410
335	Novartis Investigative Site	Lugano		Switzerland	6900
336	Novartis Investigative Site	Taichung		Taiwan	40705
337	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
338	Novartis Investigative Site	Adana		Turkey	01330
339	Novartis Investigative Site	Ankara		Turkey	06100
340	Novartis Investigative Site	Bursa		Turkey	16059
341	Novartis Investigative Site	Mersin		Turkey	33343
342	Novartis Investigative Site	Yenisehir/Izmir		Turkey	35110
343	Novartis Investigative Site	Cambridge	Cambrigdeshire	United Kingdom	CB2 0QQ
344	Novartis Investigative Site	Plymouth	Devon	United Kingdom	PL6 8DH
345	Novartis Investigative Site	Chertsey	Surrey	United Kingdom	KT16 0PZ
346	Novartis Investigative Site	Bradford	West Yorkshire	United Kingdom	BD9 6RJ
347	Novartis Investigative Site	East Yorkshire		United Kingdom	HU16 5JQ
348	Novartis Investigative Site	Leicester		United Kingdom	LE3 9QP

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 21, 2020
• Study Protocol - Jan 17, 2018

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03052517
• Other Study ID Numbers: CQAW039A2315; 2016-001560-11
• First Posted: Feb 14, 2017
• Last Update Posted: Oct 12, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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 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
Pre-assignment Detail	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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Period Title: Overall Study
STARTED	1093	1085	360
Safety Set (SAF)	1092	1084	361
COMPLETED	76	71	32
NOT COMPLETED	1017	1014	328

Baseline Characteristics

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo	Total
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily	Total of all reporting groups
Overall Participants	1092	1084	361	2537
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.1 (14.95)	50.1 (15.55)	49.9 (14.99)	50.1 (15.21)
Sex: Female, Male (Count of Participants)
Female	659 60.3%	666 61.4%	229 63.4%	1554 61.3%
Male	433 39.7%	418 38.6%	132 36.6%	983 38.7%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	757 69.3%	756 69.7%	243 67.3%	1756 69.2%
Black	30 2.7%	14 1.3%	11 3%	55 2.2%
Asian	219 20.1%	215 19.8%	73 20.2%	507 20%
Native American	27 2.5%	40 3.7%	12 3.3%	79 3.1%
Pacific Islander	0 0%	1 0.1%	0 0%	1 0%
Unknown	0 0%	9 0.8%	2 0.6%	11 0.4%
Other	59 5.4%	49 4.5%	20 5.5%	128 5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 52 - Cox Regression Model
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	675 61.8%	654 60.3%	237 65.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.72 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

2. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) up to Week 156 - Cox Regression Model
Description	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
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	709 64.9%	681 62.8%	243 67.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.73 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

3. Primary Outcome

Title	Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 52 - Cox Regression Model
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	73 6.7%	53 4.9%	29 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

4. Primary Outcome

Title	Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) up to Week 156 - Cox Regression Model
Description	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.
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	86 7.9%	63 5.8%	33 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

5. Primary Outcome

Title	Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 52 - Cox Regression Model
Description	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.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	26 2.4%	33 3%	9 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.47 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; 0.70 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

6. Primary Outcome

Title	Number of Participants With Treatment Emergent AEs Leading to Discontinuation From Study Treatment up to Week 156 - Cox Regression Model
Description	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
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Count of Participants [Participants]	30 2.7%	37 3.4%	9 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Hazard Ratio = QAW039 150mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.56 to 2.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Hazard Ratio = QAW039 450mg / Placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.67 to 2.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Hazard Ratio = QAW039 450mg / QAW039 150mg
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	A hazard ratio < 1 favors the treatment group in the numerator of the ratio.

7. Secondary Outcome

Title	Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 52 - Logistic Regression Model
Description	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)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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 Logistic regression model were included

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Number of patients with at least one AE	675 61.8%	654 60.3%	237 65.7%
Blood and lymphatic system disorders	21 1.9%	10 0.9%	5 1.4%
Cardiac disorders	11 1%	26 2.4%	7 1.9%
Congenital, familial and genetic disorders	1 0.1%	3 0.3%	0 0%
Ear and labyrinth disorders	16 1.5%	9 0.8%	8 2.2%
Endocrine disorders	2 0.2%	6 0.6%	0 0%
Eye disorders	13 1.2%	11 1%	9 2.5%
Gastrointestinal disorders	88 8.1%	86 7.9%	32 8.9%
General disorders & administration site conditions	38 3.5%	33 3%	7 1.9%
Hepatobiliary disorders	9 0.8%	17 1.6%	7 1.9%
Immune system disorders	11 1%	10 0.9%	6 1.7%
Infections and infestations	400 36.6%	374 34.5%	145 40.2%
Injury, poisoning and procedural complications	67 6.1%	52 4.8%	23 6.4%
Investigations	79 7.2%	85 7.8%	20 5.5%
Metabolism and nutrition disorders	53 4.9%	50 4.6%	21 5.8%
Musculoskeletal and connective tissue disorders	91 8.3%	84 7.7%	24 6.6%
Neoplasms benign, malignant and unspecified	13 1.2%	9 0.8%	3 0.8%
Nervous system disorders	67 6.1%	73 6.7%	29 8%
Product issues	1 0.1%	0 0%	0 0%
Psychiatric disorders	18 1.6%	15 1.4%	9 2.5%
Renal and urinary disorders	33 3%	41 3.8%	8 2.2%
Reproductive system and breast disorders	14 1.3%	9 0.8%	4 1.1%
Respiratory, thoracic and mediastinal disorders	308 28.2%	304 28%	135 37.4%
Skin and subcutaneous tissue disorders	38 3.5%	39 3.6%	13 3.6%
Social circumstances	1 0.1%	1 0.1%	3 0.8%
Vascular disorders	39 3.6%	33 3%	9 2.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 150mg /Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.626 to 1.047
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 450mg /Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.622 to 1.038
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 450mg /QAW039 150mg
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.821 to 1.200
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Patients With at Least One Treatment Emergent AE by Primary System Organ Class up to Week 156 - Logistic Regression Model
Description	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)
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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 Logistic regression model were included.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1081	1077	359
Number of patients with at least one AE	710 65%	682 62.9%	243 67.3%
Blood and lymphatic system disorders	23 2.1%	12 1.1%	5 1.4%
Cardiac disorders	16 1.5%	34 3.1%	7 1.9%
Congenital, familial and genetic disorders	1 0.1%	3 0.3%	1 0.3%
Ear and labyrinth disorders	18 1.6%	13 1.2%	9 2.5%
Endocrine disorders	5 0.5%	7 0.6%	0 0%
Eye disorders	16 1.5%	14 1.3%	9 2.5%
Gastrointestinal disorders	101 9.2%	96 8.9%	38 10.5%
General disorders & administration site conditions	43 3.9%	34 3.1%	8 2.2%
Hepatobiliary disorders	10 0.9%	21 1.9%	8 2.2%
Immune system disorders	11 1%	11 1%	6 1.7%
Infections and infestations	436 39.9%	415 38.3%	151 41.8%
Injury, poisoning and procedural complications	80 7.3%	63 5.8%	28 7.8%
Investigations	90 8.2%	102 9.4%	24 6.6%
Metabolism and nutrition disorders	61 5.6%	60 5.5%	23 6.4%
Musculoskeletal and connective tissue disorders	102 9.3%	92 8.5%	31 8.6%
Neoplasms benign, malignant and unspecified	17 1.6%	11 1%	3 0.8%
Nervous system disorders	83 7.6%	77 7.1%	32 8.9%
Pregnancy, puerperium and perinatal conditions	1 0.1%	0 0%	0 0%
Product issues	1 0.1%	0 0%	0 0%
Psychiatric disorders	23 2.1%	18 1.7%	9 2.5%
Renal and urinary disorders	36 3.3%	45 4.2%	10 2.8%
Reproductive system and breast disorders	17 1.6%	10 0.9%	4 1.1%
Respiratory, thoracic and mediastinal disorders	336 30.8%	341 31.5%	144 39.9%
Skin and subcutaneous tissue disorders	45 4.1%	45 4.2%	15 4.2%
Social circumstances	1 0.1%	1 0.1%	3 0.8%
Vascular disorders	45 4.1%	40 3.7%	13 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, Placebo
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 150mg /Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.667 to 1.125
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	QAW039 450 mg, Placebo
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 450mg /Placebo
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.643 to 1.082
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	QAW039 150mg, QAW039 450 mg
	Comments	Statistical Analysis for Number of patients with at least one AE. Hazard Ratio = QAW039 450mg /QAW039 150mg
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.794 to 1.167
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 52
Description	The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1092	1084	361
Number [Number of deaths]	0	0	0

10. Secondary Outcome

Title	Number of Treatment Emergent Patient Deaths Due to an Asthma Exacerbation up to Week 156
Description	The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1092	1084	361
Number [Number of deaths]	0	0	0

11. Secondary Outcome

Title	Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 52
Description	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
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1092	1084	361
Number [Hospitalizations per person year]	0.04	0.02	0.06

12. Secondary Outcome

Title	Rate of Treatment Emergent Severe Asthma Exacerbation Episodes Requiring Hospitalizations Per Person Year up to Week 156
Description	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
Time Frame	156 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	QAW039 150mg	QAW039 450 mg	Placebo
Arm/Group Description	QAW039 Dose 1 once daily	QAW039 Dose 2 once daily	Placebo once daily
Measure Participants	1092	1084	361
Number [Hospitalizations per person year]	0.04	0.02	0.05

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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).
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	3/1092 (0.3%)		1/1084 (0.1%)		1/361 (0.3%)
Serious Adverse Events
	QAW039 150 mg		QAW039 450 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/1092 (8%)		64/1084 (5.9%)		33/361 (9.1%)
Blood and lymphatic system disorders
Blood loss anaemia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Cardiac disorders
Angina pectoris	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Angina unstable	2/1092 (0.2%)		1/1084 (0.1%)		0/361 (0%)
Arteriosclerosis coronary artery	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Atrial fibrillation	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Cardiac failure	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Mitral valve incompetence	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Myocardial infarction	0/1092 (0%)		2/1084 (0.2%)		0/361 (0%)
Pericardial effusion	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Ventricular extrasystoles	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Ventricular tachycardia	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Congenital, familial and genetic disorders
Fibrous dysplasia of bone	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Skeletal dysplasia	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Ear and labyrinth disorders
Meniere's disease	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Tympanic membrane perforation	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Vertigo	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Gastrointestinal disorders
Abdominal hernia	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Abdominal pain	1/1092 (0.1%)		1/1084 (0.1%)		1/361 (0.3%)
Diarrhoea	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Dyspepsia	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Gastritis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Haemorrhoids	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Intestinal obstruction	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Large intestinal obstruction	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Melaena	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Pancreatitis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Pancreatitis acute	0/1092 (0%)		1/1084 (0.1%)		2/361 (0.6%)
Peritoneal cyst	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Peritoneal haemorrhage	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Strangulated umbilical hernia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
General disorders
Death	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Fatigue	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Hyperplasia	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Non-cardiac chest pain	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Pain	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Swelling face	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Hepatobiliary disorders
Cholecystitis	0/1092 (0%)		2/1084 (0.2%)		0/361 (0%)
Cholelithiasis	2/1092 (0.2%)		1/1084 (0.1%)		0/361 (0%)
Immune system disorders
Eosinophilic granulomatosis with polyangiitis	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Infections and infestations
Acute sinusitis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Bacterial infection	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Bronchitis	0/1092 (0%)		3/1084 (0.3%)		0/361 (0%)
Bronchitis bacterial	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Cellulitis	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Chronic sinusitis	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Dengue fever	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Dengue haemorrhagic fever	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Diverticulitis	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Influenza	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Lung abscess	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Otitis media	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Pneumonia	7/1092 (0.6%)		4/1084 (0.4%)		2/361 (0.6%)
Pneumonia bacterial	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Pyelonephritis acute	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Rectal abscess	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Respiratory tract infection	2/1092 (0.2%)		0/1084 (0%)		1/361 (0.3%)
Rhinitis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Septic shock	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Sinusitis	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Tuberculosis	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Upper respiratory tract infection bacterial	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Urinary tract infection	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Urosepsis	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Vaginal abscess	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Viral upper respiratory tract infection	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Exposure to allergen	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Fall	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Femur fracture	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Foot fracture	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Fracture displacement	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Humerus fracture	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Joint injury	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Lumbar vertebral fracture	0/1092 (0%)		1/1084 (0.1%)		1/361 (0.3%)
Multiple injuries	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Radius fracture	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Rib fracture	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Road traffic accident	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Skeletal injury	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Upper limb fracture	1/1092 (0.1%)		1/1084 (0.1%)		1/361 (0.3%)
Wrist fracture	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Investigations
Electrocardiogram Q wave abnormal	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Electrocardiogram T wave inversion	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Oxygen saturation decreased	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Hyperlipidaemia	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Arthritis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Back pain	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Intervertebral disc degeneration	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Intervertebral disc protrusion	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Muscular weakness	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Basal cell carcinoma	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Breast cancer	2/1092 (0.2%)		0/1084 (0%)		0/361 (0%)
Cervix carcinoma	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Gastric cancer	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Intraductal proliferative breast lesion	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Lung neoplasm malignant	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Malignant melanoma	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Myeloproliferative neoplasm	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Prostate cancer	0/1092 (0%)		1/1084 (0.1%)		1/361 (0.3%)
Rectal neoplasm	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Renal cancer	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Tongue neoplasm malignant stage unspecified	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Transitional cell carcinoma	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Uterine leiomyoma	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Nervous system disorders
Brain stem haemorrhage	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Cerebral infarction	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Cerebral ischaemia	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Cerebrovascular accident	0/1092 (0%)		2/1084 (0.2%)		0/361 (0%)
Colloid brain cyst	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Dyspraxia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Facial paralysis	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Guillain-Barre syndrome	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Headache	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Ischaemic stroke	3/1092 (0.3%)		0/1084 (0%)		2/361 (0.6%)
Loss of consciousness	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Lumbar radiculopathy	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Psychiatric disorders
Depression	3/1092 (0.3%)		1/1084 (0.1%)		0/361 (0%)
Renal and urinary disorders
Acute kidney injury	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Calculus urinary	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Chronic kidney disease	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Nephrolithiasis	0/1092 (0%)		2/1084 (0.2%)		1/361 (0.3%)
Renal failure	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Ureterolithiasis	0/1092 (0%)		1/1084 (0.1%)		0/361 (0%)
Reproductive system and breast disorders
Endometrial hyperplasia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Uterine polyp	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Respiratory, thoracic and mediastinal disorders
Aphonia	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Asthma	30/1092 (2.7%)		16/1084 (1.5%)		13/361 (3.6%)
Diaphragmatic paralysis	0/1092 (0%)		0/1084 (0%)		1/361 (0.3%)
Dyspnoea	1/1092 (0.1%)		0/1084 (0%)		1/361 (0.3%)
Pleural effusion	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (0%)
Pulmonary embolism	1/1092 (0.1%)		2/1084 (0.2%)		0/361 (0%)
Pulmonary mass	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Wheezing	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Vascular disorders
Aortic stenosis	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Deep vein thrombosis	1/1092 (0.1%)		0/1084 (0%)		0/361 (0%)
Hypertension	1/1092 (0.1%)		1/1084 (0.1%)		0/361 (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	525/1092 (48.1%)		499/1084 (46%)		190/361 (52.6%)
Infections and infestations
Bronchitis	75/1092 (6.9%)		55/1084 (5.1%)		38/361 (10.5%)
Influenza	30/1092 (2.7%)		28/1084 (2.6%)		9/361 (2.5%)
Nasopharyngitis	110/1092 (10.1%)		106/1084 (9.8%)		36/361 (10%)
Pharyngitis	34/1092 (3.1%)		22/1084 (2%)		15/361 (4.2%)
Sinusitis	39/1092 (3.6%)		28/1084 (2.6%)		9/361 (2.5%)
Upper respiratory tract infection	72/1092 (6.6%)		43/1084 (4%)		25/361 (6.9%)
Upper respiratory tract infection bacterial	14/1092 (1.3%)		31/1084 (2.9%)		12/361 (3.3%)
Urinary tract infection	23/1092 (2.1%)		37/1084 (3.4%)		11/361 (3%)
Viral upper respiratory tract infection	34/1092 (3.1%)		31/1084 (2.9%)		9/361 (2.5%)
Investigations
Blood creatinine increased	30/1092 (2.7%)		42/1084 (3.9%)		2/361 (0.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	22/1092 (2%)		11/1084 (1%)		8/361 (2.2%)
Back pain	29/1092 (2.7%)		31/1084 (2.9%)		10/361 (2.8%)
Nervous system disorders
Headache	41/1092 (3.8%)		29/1084 (2.7%)		24/361 (6.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	291/1092 (26.6%)		275/1084 (25.4%)		125/361 (34.6%)
Rhinitis allergic	19/1092 (1.7%)		28/1084 (2.6%)		11/361 (3%)
Vascular disorders
Hypertension	30/1092 (2.7%)		30/1084 (2.8%)		11/361 (3%)

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.