Dose Finding Study for QAW039 in Asthma

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01437735

Collaborator

(none)

1,043

Enrollment

206

Locations

Arms

Duration (Months)

5.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to demonstrate a clinically significant improvement in Forced Expiratory Volume in one second (FEV1) in moderate to severe allergic asthmatics inadequately controlled by Inhaled Corticosteroid (ICS) therapy. Patients will be treated with QAW039, an active comparator, or placebo. This will be a randomized, placebo-controlled, dose-ranging, multi-centre trial.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: QAW039 Drug: Montelukast Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

1043 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Placebo-controlled, Dose-ranging, Multi-centre Trial of QAW039 (1-450 mg p.o.), to Investigate the Effect on FEV1 and ACQ in Patients With Moderate-to-severe, Persistent, Allergic Asthma, Inadequately Controlled With ICS Therapy.

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Nov 1, 2013

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QAW039 po dose 1	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 2	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 3	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 4	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 5	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 6	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 7	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 8	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 9	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 10	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 11	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 12	Drug: QAW039 QAW039 po
Experimental: QAW039 po dose 13	Drug: QAW039 QAW039 po
Active Comparator: Montelukast po 10 mg Comparator leukotriene receptor antagonist (LRTA)	Drug: Montelukast Montelukast 10 mg po
Placebo Comparator: Placebo	Drug: Placebo Placebo

Outcome Measures

Primary Outcome Measures

Change in trough Forced Expiratory Volume in 1 second (FEV1) from baseline to week 12 [Baseline and week 12]
Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the trough measurement is taken 24 hours after morning dose on the previous day.

Secondary Outcome Measures

Change in Asthma Control Questionnaire (ACQ) score from baseline to week 12 [Baseline and week 12]
The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Change in Forced Expiratory Volume in 1 second (FEV1) from baseline to weeks 2, 4 and 8. [Baseline, week 2, week 4 and week 8]
Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.
Change in the Asthma Control Questionnaire (ACQ) score from baseline to weeks 2, 4 and 8. [Baseline, week 2, week 4 and week 8]
The Asthma Control Questionnaire (ACQ) is a validated questionnaire consisting of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 assessing the patients Forced Expiratory Volume in 1 second (FEV1) result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Change in the dose response relationship among QAW039 doses with respect to Forced Expiratory Volume in 1 second (FEV1) after 12 weeks treatment. [Baseline and week 12]
Forced Expiratory Volume in 1 second (FEV1) (measured in litters), and the measurement is taken 24 hours after the morning dose on the previous day.
Comparison of vital signs, ECG, laboratory tests and adverse events across QAW039 doses and placebo. [Baseline and week 12]
Comparisons of vital signs (i.e. systolic and diastolic blood pressure, pulse rate), ECG (e.g. quantitative assessments - heart rate, QTcF, PRS, PR intervals), laboratory tests (haematology, clinical chemistry and urinalysis) and adverse events across QAW039 doses and placebo.
Comparison of efficacy of QAW039 with that of active comparator as an add-on therapy to Inhaled Corticosteroids (ICS) [Baseline and week 12]
Forced Expiratory Volume in 1 second (FEV1) measurement taken 24 hours after the morning dose on the previous day. The Asthma Control Questionnaire (ACQ)consisting of 7 items: 5 on system assessment, 1 on rescue bronchodilator use and 1 assessing the patients for FEV1 result against the predicted result for a person of similar age and stature. Each item is graded on a scale of 0-6, and a mean score of 1.5 or greater is considered to demonstrate inadequate asthma control in this trial. The minimal important difference that is considered clinically important is a change of 0.5 in the mean score.
Assess the effect of QAW039 on asthma symptoms as measured by asthma control diary. [Baseline and week 12]
The asthma control diary mimics the Asthma Control Questionnaire (ACQ), but is recorded daily by the patient, rather than at each visit. As for the ACQ, the ACD consists of 7 questions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Physician diagnosis of asthma, as per the Global Initiative for Asthma (GINA) (2009) guidelines, and currently prescribed Inhaled Corticosteroids (ICS) therapy.
Patients with a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) value of 40% to 80% of individual predicted value.
Patients should be allergic or atopic, as diagnosed historically or prior to entry into the study.
Patients who are demonstrated to have reversible airway obstruction or airways hyper-reactivity or have shown either of such responses in previous test(s) within the last year.
An Asthma Control Questionnaire (ACQ) score ≥ 1.5 at randomization.

Exclusion Criteria:

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
Patients with serious co-morbidities including uncontrolled diabetes (HbA1c≥8%), heart failure, cancer, neurodegenerative diseases, rheumatoid arthritis and other autoimmune diseases, other lung diseases including chronic bronchitis, chronic obstructive pulmonary diseases or emphysema or other conditions characterized by eosinophilia and pulmonary symptoms (i.e. Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, eosinophilic pneumonia, etc.).
Acute illness other than asthma at the start of the study
History of life-threatening asthma, including a history of significant hypercarbia (pCO2>45mmHg), prior intubation, respiratory arrest, or seizures as a result of asthma.
Patients who have had a respiratory tract infection within 4 weeks of the screening visit. Patients who develop a respiratory tract infection between screening and the randomization visit must be screen failed, and may be permitted to re-enroll at a later date.
Current smokers or ex-smokers who stopped smoking within 6 months prior to screening or have a smoking history of ≥ 10 pack years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Scottsdale	Arizona	United States	85251
2	Novartis Investigative Site	Encinitas	California	United States	92024
3	Novartis Investigative Site	Huntington Beach	California	United States	92647
4	Novartis Investigative Site	Los Angeles	California	United States	90048
5	Novartis Investigative Site	Orange	California	United States	92868
6	Novartis Investigative Site	Riverside	California	United States	92506
7	Novartis Investigative Site	San Diego	California	United States	92120
8	Novartis Investigative Site	San Diego	California	United States	92123
9	Novartis Investigative Site	San Jose	California	United States	95117
10	Novartis Investigative Site	San Mateo	California	United States	94401
11	Novartis Investigative Site	Stockton	California	United States	95207
12	Novartis Investigative Site	Centennial	Colorado	United States	80112
13	Novartis Investigative Site	Denver	Colorado	United States	80230
14	Novartis Investigative Site	Sarasota	Florida	United States	34233
15	Novartis Investigative Site	Savannah	Georgia	United States	31406
16	Novartis Investigative Site	River Forest	Illinois	United States	60305
17	Novartis Investigative Site	Bangor	Maine	United States	04401
18	Novartis Investigative Site	Wheaton	Maryland	United States	20902
19	Novartis Investigative Site	North Dartmouth	Massachusetts	United States	02747
20	Novartis Investigative Site	Minneapolis	Minnesota	United States	55402
21	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
22	Novartis Investigative Site	Warrensburg	Missouri	United States	64093
23	Novartis Investigative Site	Omaha	Nebraska	United States	68130
24	Novartis Investigative Site	Omaha	Nebraska	United States	68131
25	Novartis Investigative Site	Papillion	Nebraska	United States	68046
26	Novartis Investigative Site	Skillman	New Jersey	United States	08558
27	Novartis Investigative Site	Canton	Ohio	United States	44718
28	Novartis Investigative Site	Columbus	Ohio	United States	43213
29	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73103
30	Novartis Investigative Site	Lake Oswego	Oregon	United States	97035
31	Novartis Investigative Site	Medford	Oregon	United States	97504-8741
32	Novartis Investigative Site	Erie	Pennsylvania	United States	16507
33	Novartis Investigative Site	Lincoln	Rhode Island	United States	02865
34	Novartis Investigative Site	Charleston	South Carolina	United States	29407
35	Novartis Investigative Site	Dallas	Texas	United States	75231
36	Novartis Investigative Site	Fort Worth	Texas	United States	76132
37	Novartis Investigative Site	Waco	Texas	United States	76712
38	Novartis Investigative Site	South Burlington	Vermont	United States	05403
39	Novartis Investigative Site	Caba	Buenos Aires	Argentina	B8000XAV
40	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1122AAK
41	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1186ACB
42	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1425BEN
43	Novartis Investigative Site	Florencio Varela	Buenos Aires	Argentina	B2705XAE
44	Novartis Investigative Site	Mar del Plata	Buenos Aires	Argentina	7600
45	Novartis Investigative Site	Quilmes	Buenos Aires	Argentina	B1878FNR
46	Novartis Investigative Site	Santa Fe	Rosario	Argentina	S2000DBS
47	Novartis Investigative Site	San Miguel de Tucuman	Tucuman	Argentina	4000
48	Novartis Investigative Site	Buenos Aires		Argentina	C1115AAB
49	Novartis Investigative Site	Buenos Aires		Argentina	C1125ABE
50	Novartis Investigative Site	Mendoza		Argentina	5500
51	Novartis Investigative Site	Santa Fe		Argentina	S3000FIL
52	Novartis Investigative Site	Feldbach		Austria	8330
53	Novartis Investigative Site	Grieskirchen		Austria	4710
54	Novartis Investigative Site	Linz		Austria	4020
55	Novartis Investigative Site	Thalheim bei Wels		Austria	4600
56	Novartis Investigative Site	Vienna		Austria	1210
57	Novartis Investigative Site	Plovdiv		Bulgaria	400
58	Novartis Investigative Site	Ruse		Bulgaria	7002
59	Novartis Investigative Site	Sofia		Bulgaria	1431
60	Novartis Investigative Site	Sofia		Bulgaria	1463
61	Novartis Investigative Site	Varna		Bulgaria	9020
62	Novartis Investigative Site	Ottawa	Ontario	Canada	K1Y 4G2
63	Novartis Investigative Site	Toronto	Ontario	Canada	M4V 1R2
64	Novartis Investigative Site	Quebec		Canada	GIV 4M6
65	Novartis Investigative Site	Bogota	Cundinamarca	Colombia
66	Novartis Investigative Site	Armenia		Colombia
67	Novartis Investigative Site	Barranquilla		Colombia
68	Novartis Investigative Site	Bogotá		Colombia
69	Novartis Investigative Site	Medellín		Colombia
70	Novartis Investigative Site	Ferolles-Attily		France	77150
71	Novartis Investigative Site	Lyon cedex 04		France	69317
72	Novartis Investigative Site	Montpellier		France	34059
73	Novartis Investigative Site	Paris		France	75006
74	Novartis Investigative Site	Pessac		France	33604
75	Novartis Investigative Site	Reims		France	51092
76	Novartis Investigative Site	Strasbourg Cedex		France	67091
77	Novartis Investigative Site	Tarbes Cedex		France	65013
78	Novartis Investigative Site	Athens	GR	Greece	115 27
79	Novartis Investigative Site	Heraklion - Crete	GR	Greece	711 10
80	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
81	Novartis Investigative Site	Antigua Guatemala		Guatemala
82	Novartis Investigative Site	Guatemala City		Guatemala	01010
83	Novartis Investigative Site	Guatemala City		Guatemala	01015
84	Novartis Investigative Site	Balassagyarmat		Hungary	2660
85	Novartis Investigative Site	Debrecen		Hungary	4032
86	Novartis Investigative Site	Deszk		Hungary	6772
87	Novartis Investigative Site	Gyor		Hungary	9024
88	Novartis Investigative Site	Mosonmagyarovar		Hungary	9200
89	Novartis Investigative Site	Nyiregyhaza		Hungary	4400
90	Novartis Investigative Site	Százhalombatta		Hungary	2440
91	Novartis Investigative Site	Torokbalint		Hungary	2045
92	Novartis Investigative Site	Panjim	Goa	India	403 002
93	Novartis Investigative Site	Ahmedabad	Gujarat	India	380007
94	Novartis Investigative Site	Bangalore	Karnataka	India	560 010
95	Novartis Investigative Site	Mysore	Karnataka	India	570004
96	Novartis Investigative Site	Indore	Madhya Pradesh	India	452001
97	Novartis Investigative Site	Nagpur	Maharashtra	India	440 012
98	Novartis Investigative Site	Pune	Maharashtra	India	411 014
99	Novartis Investigative Site	Ludhiana	Punjab	India	141001
100	Novartis Investigative Site	Jaipur	Rajasthan	India	302017
101	Novartis Investigative Site	Chennai	Tamil Nadu	India	600 006
102	Novartis Investigative Site	Coimbatore	Tamil Nadu	India	641004
103	Novartis Investigative Site	Nagpur - Maharashtra		India	440012
104	Novartis Investigative Site	Firenze	FI	Italy	50134
105	Novartis Investigative Site	Pisa	PI	Italy	56124
106	Novartis Investigative Site	Parma	PR	Italy	43100
107	Novartis Investigative Site	Nishio-city	Aichi	Japan	445-8510
108	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	819-8555
109	Novartis Investigative Site	Kasuga-city	Fukuoka	Japan	816-0813
110	Novartis Investigative Site	Kitakyushu	Fukuoka	Japan	802-0083
111	Novartis Investigative Site	Kitakyushu	Fukuoka	Japan	820-0052
112	Novartis Investigative Site	Yanagawa	Fukuoka	Japan	832-0059
113	Novartis Investigative Site	Mizunami-city	Gifu	Japan	509-6134
114	Novartis Investigative Site	Hatsukaichi-city	Hiroshima	Japan	739-0402
115	Novartis Investigative Site	Asahikawa-city	Hokkaido	Japan	070-8644
116	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	060-0061
117	Novartis Investigative Site	Sapporo	Hokkaido	Japan	062-8618
118	Novartis Investigative Site	Himeji-city	Hyogo	Japan	672-8064
119	Novartis Investigative Site	Higashiibaraki-gun	Ibaraki	Japan	311-3193
120	Novartis Investigative Site	Hitachi-city	Ibaraki	Japan	317-0077
121	Novartis Investigative Site	Kanazawa	Ishikawa	Japan	920-0853
122	Novartis Investigative Site	Sakaide	Kagawa	Japan	762-0031
123	Novartis Investigative Site	Kawasaki-city	Kanagawa	Japan	210-0852
124	Novartis Investigative Site	Sagamihara-city	Kanagawa	Japan	228-8522
125	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	231-8682
126	Novartis Investigative Site	Sendai-city	Miyagi	Japan	983-8520
127	Novartis Investigative Site	Kurashiki-city	Okayama	Japan	712-8064
128	Novartis Investigative Site	Tsukubo-gun	Okayama	Japan	701-0304
129	Novartis Investigative Site	Habikino city	Osaka	Japan	583-8588
130	Novartis Investigative Site	Kishiwada	Osaka	Japan	596-8501
131	Novartis Investigative Site	Osakasayama	Osaka	Japan	589-0022
132	Novartis Investigative Site	Koshigaya-city	Saitama	Japan	343-0851
133	Novartis Investigative Site	Hamamatsu-city	Shizuoka	Japan	430-8558
134	Novartis Investigative Site	Hamamatsu	Shizuoka	Japan	430-8525
135	Novartis Investigative Site	Hamamatsu	Shizuoka	Japan	434-8511
136	Novartis Investigative Site	Chiyoda-ku	Tokyo	Japan	1020083
137	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0027
138	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	103-0028
139	Novartis Investigative Site	Edogawa-ku	Tokyo	Japan	134-0083
140	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
141	Novartis Investigative Site	Kiyose-city	Tokyo	Japan	204-8585
142	Novartis Investigative Site	Minato-ku	Tokyo	Japan	108-8606
143	Novartis Investigative Site	Setagaya-ku	Tokyo	Japan	158-0097
144	Novartis Investigative Site	Tachikawa	Tokyo	Japan	190-0013
145	Novartis Investigative Site	Taito	Tokyo	Japan	111-0052
146	Novartis Investigative Site	Toshima-ku	Tokyo	Japan	171-0014
147	Novartis Investigative Site	Fukuoka		Japan	811-1394
148	Novartis Investigative Site	Hiroshima		Japan	732-0052
149	Novartis Investigative Site	Kochi		Japan	780-8077
150	Novartis Investigative Site	Kyoto		Japan	612-0026
151	Novartis Investigative Site	Osaka		Japan	560-0005
152	Novartis Investigative Site	Mexicali	Baja California	Mexico	21100
153	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	03020
154	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	14050
155	Novartis Investigative Site	México	Distrito Federal	Mexico	14080
156	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44130
157	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44280
158	Novartis Investigative Site	Zapopan	Jalisco	Mexico	45040
159	Novartis Investigative Site	Monterrey	Nuevo León	Mexico	64718
160	Novartis Investigative Site	Almelo		Netherlands	7609 PP
161	Novartis Investigative Site	Harderwijk		Netherlands	3840 AC
162	Novartis Investigative Site	Cercado De Lima	Lima	Peru	01
163	Novartis Investigative Site	Jesus Maria	Lima	Peru	11
164	Novartis Investigative Site	Miraflores	Lima	Peru	18
165	Novartis Investigative Site	San Borja	Lima	Peru	41
166	Novartis Investigative Site	San Isidro	Lima	Peru	27
167	Novartis Investigative Site	Santiago de Surco	Lima	Peru	33
168	Novartis Investigative Site	Katowice		Poland	40-752
169	Novartis Investigative Site	Krakow		Poland	31-159
170	Novartis Investigative Site	Bucharest	District 1	Romania	10457
171	Novartis Investigative Site	Bucharest	District 1	Romania	11475
172	Novartis Investigative Site	Bucharest	District 3	Romania	030317
173	Novartis Investigative Site	Craiova	Dolj	Romania	200515
174	Novartis Investigative Site	Iasi	Jud. Iasi	Romania	700115
175	Novartis Investigative Site	Arad		Romania	310013
176	Novartis Investigative Site	Arad		Romania	310086
177	Novartis Investigative Site	Bucharest		Romania	050159
178	Novartis Investigative Site	Deva		Romania	330162
179	Novartis Investigative Site	Barnaul		Russian Federation	656024
180	Novartis Investigative Site	Barnaul		Russian Federation	656045
181	Novartis Investigative Site	Chelyabinsk		Russian Federation	454021
182	Novartis Investigative Site	Chelyabinsk		Russian Federation	454047
183	Novartis Investigative Site	Moscow		Russian Federation	119992
184	Novartis Investigative Site	Moscow		Russian Federation	125315
185	Novartis Investigative Site	Ryazan		Russian Federation	390026
186	Novartis Investigative Site	St. Petersburg		Russian Federation	194354
187	Novartis Investigative Site	St.-Petersburg		Russian Federation	193231
188	Novartis Investigative Site	Yaroslavl		Russian Federation	150003
189	Novartis Investigative Site	Amanzimtoti		South Africa	4126
190	Novartis Investigative Site	Benoni		South Africa
191	Novartis Investigative Site	Cape Town		South Africa	7531
192	Novartis Investigative Site	Cape Town		South Africa	7925
193	Novartis Investigative Site	Durban		South Africa	4001
194	Novartis Investigative Site	Gatesville		South Africa	7764
195	Novartis Investigative Site	Port Elizabeth		South Africa	6001
196	Novartis Investigative Site	Pretoria		South Africa	0001
197	Novartis Investigative Site	Pretoria		South Africa	0181
198	Novartis Investigative Site	Fatih / Istanbul		Turkey	34098
199	Novartis Investigative Site	Istanbul		Turkey	34093
200	Novartis Investigative Site	Istanbul		Turkey	34854
201	Novartis Investigative Site	Izmir		Turkey	35040
202	Novartis Investigative Site	Mersin		Turkey	33079
203	Novartis Investigative Site	Yenisehir/Izmir		Turkey	35110
204	Novartis Investigative Site	Newcastle Upon Tyne	Newcastle	United Kingdom	NE7 7DN
205	Novartis Investigative Site	Bradford		United Kingdom	BD9 6RJ
206	Novartis Investigative Site	Glasgow - Scotland		United Kingdom	G12 OYN