Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma

Asthma Clinical Trial

Official title:

A Multicenter, Randomized, 52-week, Double-blind, Parallelgroup, Active Controlled Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02571777
• Other study ID #: CQVM149B2302
• Secondary ID: 2015-002899-25
• Status: Completed
• Phase: Phase 3
• Start date: December 8, 2015
• Est. completion date: June 14, 2019

Study information

• Verified date: July 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the trial was to evaluate the efficacy and safety of two different doses of QVM149 (QVM149 150/50/80 μg and QVM149 150/50/160 μg via Concept1) over two respective QMF149 doses (QMF149 150/160 μg and QMF149 150/320) μg via Concept1 in poorly controlled asthmatics as determined by pulmonary function testing and effects on asthma control.

Description:

This study used a 52-week treatment, randomized, double-blind, double-dummy, parallel-group design. A total of 3092 asthma patients were randomized into the 5 treatment groups with a randomization ratio of 1:1:1:1:1 (approximately 617 patients per treatment group): QVM149 150/50/80 μg once daily (o.d.), QVM149 150/50/160 μg o.d., QMF149 150/160 μg o.d. and QMF149 150/320 μg o.d., all delivered via the Concept1 device, and salmeterol/fluticasone 50/500 μg twice daily (b.i.d.) delivered via Accuhaler. The 52 week treatment period was followed by a 30-day Follow-up.

The primary objective of this study was to demonstrate superiority of either QVM149 150/50/80 μg o.d. to QMF149 150/160 μg o.d. or QVM149 150/50/160 μg o.d. to QMF149 150/320 μg o.d in terms of trough Forced Expiratory Volume in One Second (Trough FEV1) (FEV1) at Week 26, all delivered via Concept1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3092
• Est. completion date: June 14, 2019
• Est. primary completion date: June 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of asthma, (GINA 2015) for a period of at least 1 year prior to Visit 1 (Screening).

• Patients who have used medium or high dose of ICS/LABA combinations for asthma for at least 3 months and at stable medium or high doses of ICS/LABA for at least 1 month prior to Visit 1.

• Patients must be symptomatic at screening despite treatment with mid or high stable doses of ICS/LABA. Patients with ACQ-7 score = 1.5 at Visit 101 and at Visit 102 (before randomization).

• Patients with documented history of at least one asthma exacerbation which required medical care from a physician, ER visit (or local equivalent structure) or hospitalization in the 12 months prior to Visit 1, and required systemic corticosteroid treatment.

• Pre-bronchodilator FEV1 of < 80 % of the predicted normal value for the patient according to ATS/ERS guidelines after withholding bronchodilators at both visits 101 and 102.

• Withholding period of bronchodilators prior to spirometry: SABA for = 6 hrs, Twice daily LABA (or FDC of ICS/LABA) for = 12 hrs, Once daily LABA (or FDC of ICS/LABA) for = 24 hrs, SAMA for = 8 hrs, Short acting xanthines for 12 hrs, Long acting xanthines for 24 hrs, .

• Washout period of each drug should be kept as close as possible as above and should not be longer. If longer washout period is needed due to scheduling issues, please contact Novartis Medical monitor.

• A one-time repeat of percentage predicated FEV1 (Pre-bronchodilator) at Visit 101 and/or Visit 102 is allowed in an ad-hoc visit. Repeat of Visit 101 spirometry should be done in an ad-hoc visit to be scheduled on a date that would provide sufficient time to receive confirmation from the spirometry data central reviewer of the validity of the assessment before randomization. Run-in medication should be dispensed once spirometry assessment met inclusion criteria (ATS/ERS quality criteria, FEV1 % predicted normal value, and reversibility) as per equipment

• A one-time rescreen is allowed in case the patient fails to meet the criteria at the repeat, provided the patient returned to the required treatment as per inclusion criteria 4

• Patients who demonstrate an increase in FEV1 of 12% and 200 mL within 30 minutes after administration of 400 µg salbutamol/360 µg albuterol (or equivalent dose) at Visit 101.All patients must perform a reversibility test at Visit 101. If reversibility is not demonstrated at Visit 101 then one of the following criteria need to be met.

• Reversibility should be repeated once.

• Patients may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within 2 years prior to Visit 1.

• Alternatively, patients may be permitted to enter the study with a historical positive bronchoprovocation test that was performed within 2 years prior to Visit 1. If reversibility is not demonstrated at Visit 101 (or after repeated assessment in an ad-hoc visit) and historical evidence of reversibility/bronchoprovocation is not available (or was not performed according to the ATS/ERS guidelines patients must be screen failed

• Spacer devices are permitted during reversibility testing only. The Investigator or delegate may decide whether or not to use a spacer for the reversibility testing

Exclusion Criteria:

• Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening). If patients experience an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit between Visit 1 and Visit 102 they may be re-screened 6 weeks after recovery from the exacerbation.

• Patients who have ever required intubation for a severe asthma attack/exacerbation.

• Patients who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator's medical judgment at risk participating in the study.

• Patients treated with a LAMA for asthma within 3 months prior Visit 1 (Screening).

• Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered).

• Patients who have had a respiratory tract infection or asthma worsening as determined by investigator within 4 weeks prior to Visit 1 (Screening) or between Visit 1 and Visit 102. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.

• Patients with evidence upon visual inspection (laboratory culture is not required) of clinically significant (in the opinion of investigator) oropharyngeal candidiasis at Visit 102 or earlier, with or without treatment. Patients may be re-screened once their candidiasis has been treated and has resolved.

• Patients with any chronic conditions affecting the upper respiratory tract (e.g. chronic sinusitis) which in the opinion of the investigator may interfere with the study evaluation or optimal participation in the study.

• Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis.

• Patients with Type I diabetes or uncontrolled Type II diabetes.

• Patients who, either in the judgment of the investigator or the responsible Novartis personnel, have a clinically significant condition such as (but not limited to) unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure arrhythmia, uncontrolled hypertension, cerebrovascular disease, psychiatric disease, neurodegenerative diseases, or other neurological disease, uncontrolled hypo- and hyperthyroidism and other autoimmune diseases, hypokalemia, hyperadrenergic state, or ophthalmologic disorder or patients with a medical condition that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.

• Patients with paroxysmal (e.g., intermittent) atrial fibrillation are excluded. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blockers, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at the run-in visit (Visit 101) with a resting ventricular rate < 100/min. At Visit 101 the atrial fibrillation must be confirmed by central reading.

• Patients with a history of myocardial infarction (this should be confirmed clinically by the investigator) within the previous 12 months.

• Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study

• Patients with a history of long QT syndrome or whose QTc measured at Visit 101 (Fridericia method) is prolonged (> 450 msec for males and > 460 msec for females) and confirmed by a central assessor (these patients should not be rescreened).

• Patients with a history of hypersensitivity to lactose, any of the study drugs or to similar drugs within the class including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.

• Patients who have not achieved an acceptable spirometry result at Visit 101 in accordance with ATS/ERS criteria for acceptability and repeatability. A one-time repeat spirometry is allowed in an ad-hoc visit scheduled as close as possible from the first attempt (but not on the same day) if the spirometry did not qualify due to ATS/ERS criteria at Visit 101 and/or Visit 102. If the patient fails the repeat assessment, the patient may be rescreened once, provided the patient returns to the required treatment as per inclusion criteria 4.

• Patients unable to use the Concept1 dry powder inhaler, Accuhaler or a metered dose inhaler. Spacer devices are not permitted.

• History of alcohol or other substance abuse.

• Patients with a known history of non-compliance to medication or who were unable or unwilling to complete a patient diary or who are unable or unwilling to use Electronic Peak Flow with e-diary device.

• Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers).

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• QVM149 150/50/160

• QVM149 150/50/80

• QMF149 150/320

• QMF149 150/160

• salmeterol/fluticasone

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bahia Blanca	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Concepcion del Uruguay	Entre Rios
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Florida	Buenos Aires
Argentina	Novartis Investigative Site	Godoy Cruz	Mendoza
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Nueve de Julio	Buenos Aires
Argentina	Novartis Investigative Site	Parana
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	San Nicolas	Buenos Aires
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Argentina	Novartis Investigative Site	Vicente Lopez	Buenos Aires
Argentina	Novartis Investigative Site	Villa Maria	Cordoba
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Belgium	Novartis Investigative Site	Hasselt	BEL
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Belgium	Novartis Investigative Site	Lebbeke
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Malmedy
Bulgaria	Novartis Investigative Site	Plovdiv	BGR
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Canada	Novartis Investigative Site	Quebec
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China	Novartis Investigative Site	Shanghai	Shanghai
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China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenyang	Liaoning
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Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
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Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Balassagyarmat
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Hungary	Novartis Investigative Site	Szeged
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India	Novartis Investigative Site	Ahmedabad	Gujarat
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India	Novartis Investigative Site	Bangalore	Karnataka
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India	Novartis Investigative Site	Gurgaon	Haryana
India	Novartis Investigative Site	Hubli	Karnataka
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Kanpur	Uttar Pradesh
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Kozhikode	Kerala
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Mohali	Punjab
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Mysore	Karnataka
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nashik	Maharastra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Patna	Bihar
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vellore	Tamil Nadu
India	Novartis Investigative Site	Vijayawada	Andhra Pradesh
India	Novartis Investigative Site	Vishakhapatnam	Andhra Pradesh
Ireland	Novartis Investigative Site	Dublin
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Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Beer-Sheva
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel Giborim, Holon
Italy	Novartis Investigative Site	Ancona
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Catanzaro	CZ
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Messina
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Pordenone
Italy	Novartis Investigative Site	Roma
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Himeji-city	Hyogo
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kasuga-city	Fukuoka
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kishiwada-city	Osaka
Japan	Novartis Investigative Site	Kokubunji-city	Tokyo
Japan	Novartis Investigative Site	Kurashiki-city	Okayama
Japan	Novartis Investigative Site	Naka-gun	Ibaraki
Japan	Novartis Investigative Site	Obihiro-city	Hokkaido
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Tokyo	Shibuya Ku
Japan	Novartis Investigative Site	Tomakomai-city	Hokkaido
Japan	Novartis Investigative Site	Toshima ku	Tokyo
Japan	Novartis Investigative Site	Yokkaichi-city	Mie
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Jordan	Novartis Investigative Site	Amman	JOR
Jordan	Novartis Investigative Site	Amman	JOR
Latvia	Novartis Investigative Site	Balvi	LVA
Latvia	Novartis Investigative Site	Bauska	LVA
Latvia	Novartis Investigative Site	Daugavpils	LVA
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Jurmala	LVA
Latvia	Novartis Investigative Site	Rezekne	LVA
Latvia	Novartis Investigative Site	Riga	LVA
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	El Chouf	LBN
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Kaunas	LT
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Siauliai
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius	LT
Lithuania	Novartis Investigative Site	Vilnius	LTU
Mexico	Novartis Investigative Site	Culiacan	MEX
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Monterrey	Nuevo Leon
Mexico	Novartis Investigative Site	Oaxaca
Mexico	Novartis Investigative Site	Veracruz
Mexico	Novartis Investigative Site	Zapopan	Jalisco
Netherlands	Novartis Investigative Site	Breda	CK
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Harderwijk
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Helmond
Netherlands	Novartis Investigative Site	Hengelo
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Zutphen
Peru	Novartis Investigative Site	Cercado De Lima	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Peru	Novartis Investigative Site	San Miguel	Lima
Philippines	Novartis Investigative Site	Bulacan
Philippines	Novartis Investigative Site	Lipa City	Batangas
Philippines	Novartis Investigative Site	Manila	Metro Manila
Philippines	Novartis Investigative Site	Manila
Philippines	Novartis Investigative Site	Quezon City
Poland	Novartis Investigative Site	Aleksandrow Odzki
Poland	Novartis Investigative Site	Bielsko-Biala
Poland	Novartis Investigative Site	Elblag
Poland	Novartis Investigative Site	Inowroclaw
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Ksawerow	POL
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Ostrow Wielkopolski
Poland	Novartis Investigative Site	Sopot
Poland	Novartis Investigative Site	Wejherowo	POL
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Zawadzkie
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Arad
Romania	Novartis Investigative Site	Bacau
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Constanta
Romania	Novartis Investigative Site	Craiova	ROM
Romania	Novartis Investigative Site	Deva	ROM
Romania	Novartis Investigative Site	Deva
Romania	Novartis Investigative Site	Pitesti
Romania	Novartis Investigative Site	Timisoara	Timis
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ivanovo
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	Perm
Russian Federation	Novartis Investigative Site	Perm
Russian Federation	Novartis Investigative Site	Pskov
Russian Federation	Novartis Investigative Site	Pyatigorsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Tomsk
Russian Federation	Novartis Investigative Site	Tver
Russian Federation	Novartis Investigative Site	Ufa
Russian Federation	Novartis Investigative Site	Ulyanovsk
Russian Federation	Novartis Investigative Site	Vladikavkaz
Russian Federation	Novartis Investigative Site	Volgograd
Russian Federation	Novartis Investigative Site	Vsevolozhsk
Russian Federation	Novartis Investigative Site	Yaroslavl
Russian Federation	Novartis Investigative Site	Yaroslavl
Slovakia	Novartis Investigative Site	Kezmarok
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Liptovsky Mikulas
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Spisska Nova Ves
Slovakia	Novartis Investigative Site	Trencin
Slovakia	Novartis Investigative Site	Zilina
Slovakia	Novartis Investigative Site	Zvolen
South Africa	Novartis Investigative Site	Berea	Durban
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Durban	Kwazulu Natal
South Africa	Novartis Investigative Site	Kempton Park	ZAF
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	Esparraguera	Barcelona
Spain	Novartis Investigative Site	Girona	Catalunya
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Laredo	Cantabria
Spain	Novartis Investigative Site	Leon
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Marbella	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vila-real	Castellon
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Lidingo
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Gossau
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Muang	Nonthaburi
United Kingdom	Novartis Investigative Site	East Yorkshire
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Wiltshire
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Jordan,  Latvia,  Lebanon,  Lithuania,  Mexico,  Netherlands,  Peru,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Thailand,  United Kingdom,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus QMF149 at Week 26	Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.; The primary endpoint considered the following 2 comparison groups: QVM149 150/50/80 µg o.d. compared with QMF149 150/160 µg o.d. both delivered via Concept1; QVM149 150/50/160 µg o.d. compared with QMF149 150/320 µg o.d. both delivered via Concept1.	26 weeks
Secondary	Asthma Control Questionnaire (ACQ-7) at Week 26 and Week 52	The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The ACQ-7 total score reported below was calculated as the mean of scores of all 7 items and ranged between 0 and 6, with higher scores indicating worse asthma symptom control.	26 weeks, 52 weeks
Secondary	Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus Salmeterol/Fluticasone at Week 26	Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.; This secondary endpoint considered the following 2 comparison groups: QVM149 150/50/80 µg o.d. via Concept1 compared with salmeterol/fluticasone 50/500 µg b.i.d. via Accuhaler®; QVM149 150/50/160 µg o.d. via Concept 1 compared with salmeterol/fluticasone 50/500 µg b.i.d. via Accuhaler®	26 weeks
Secondary	Trough FEV1 at Week 52	Trough FEV1 was assessed by performing spirometric assessment. It is defined as average of the two FEV1 measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.	52 weeks
Secondary	Pre-dose Forced Vital Capacity (FVC) at Week 4 and Week 12	Pre-dose FVC is defined as average of the two FVC measurements taken 45 min and 15 min pre evening dose. It was assessed by performing spirometric assessment. FVC is the total amount of air exhaled during the FEV test.	4 weeks, 12 weeks
Secondary	Trough Forced Expiratory Flow (FEF) Between 25% and 75% of FVC (FEF25-75) at 52 Weeks	FEF is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration. Trough FEF25-75% is defined as average of the two FEF25-75% measurements taken 23 hr 15 min and 23 hr 45 min post-evening dose. It was assessed by performing spirometric assessment.	Up to Week 52
Secondary	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment	PEF is a person's maximum speed of expiration. All the participants were instructed to record PEF twice daily using a mini Peak Flow Meter device, once in the morning (before taking the morning dose) and once approximately 12 h later in the evening (before taking the evening dose) at home. At each timepoint, the participant was instructed to perform 3 consecutive manoeuvres within 10 minutes. These PEF values were captured in the e-PEF/diary. The best of 3 values were used.	Baseline, 26 weeks, 52 weeks
Secondary	Change From Baseline in Percentage of Asthma Symptom-free Days Over 52 Weeks	All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. Asthma symptoms free days are days with no daytime symptoms, no night-time awakenings and no symptoms on awakening. The daytime asthma symptom score was based on the daily e-diary recordings by participants with respect to shortness of breath, wheeze, cough, chest tightness, and impact on usual daily activities due to symptoms.	Baseline, 52 weeks
Secondary	Change From Baseline in Percentage of Days With no Daytime Symptoms Over 52 Weeks	All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. For days with no daytime symptoms, all 5 evening questions must have a score = 0 with respect to shortness of breath, wheeze, cough, chest tightness and impact on usual daily activities due to symptoms, each with scores from 0 (no problems) to 4 (very severe problems).	Baseline, 52 weeks
Secondary	Change From Baseline in Percentage of Nights With no Night-time Awakenings Over 52 Weeks	All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for nights with no night-time awakenings was "How did you sleep last night?" had to be answered with "I did not wake up because of any breathing problems" with scores from 0 (no problem)-4 (very severe problems).	Baseline, 52 weeks
Secondary	Change From Baseline in Percentage of Mornings With no Symptoms on Rising Over 52 Weeks	All participants were provided with an electronic diary (e-Diary) to record clinical symptoms. They were instructed to routinely complete the e-Diary twice daily at the same time each morning and again approximately 12 hours later in the evening. The e-Diary was reviewed at each visit until study completion. The question asked for nights with no night-time awakenings was "How did you sleep last night?" had to be answered with "I did not wake up because of any breathing problems" with scores from 0 (no problem)-4 (very severe problems).	Baseline, 52 weeks
Secondary	Change From Baseline in Percentage of Days Without Rescue Medication Use Over 26 and 52 Weeks	Percentage of days without rescue medication usage (100 µg salbutamol/90 µg albuterol via metered-dose inhaler) as recorded by e-diary over 26 and 52 weeks of treatment.	Baseline, 26 weeks, 52 weeks
Secondary	Percentage of Patients Achieving the Minimal Clinically Important Difference (MCID) ACQ = 0.5 at Week 26 and Week 52	Change from baseline in ACQ-7 scores of = 0.5 was defined as minimal clinically important difference and were considered clinically meaningful. The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue bronchodilator use and 1 on airway calibre (FEV1 % predicted). All 7 questions of the ACQ-7 were equally weighted. Items 1-5 were scored along a 7-point response scale, where 0 = totally controlled and 6 = severely uncontrolled. Item 6 is scored between 0 = no rescue medication and 6 = More than 16 puffs/inhalations most days. The 7th item was scored by the investigator based on the FEV1 % predicted from the masterscope at the site (i.e., Score = 0 means > 95% of predicted FEV1, 1 = 90 - 95%, 2 = 80 - 89%, 3 = 70 - 79%, 4 = 60 - 69%, 5 = 50 - 59%, and Score = 6 means < 50% of predicted FEV1). The total score was calculated as the mean of all questions.	26 weeks, 52 weeks
Secondary	Time to First Hospitalization for Asthma Exacerbation	Time from start of treatment until the first event (hospitalization for asthma exacerbation) or censoring. Patients without the event were considered as censored at the date of last treatment + 1 day. For patients having the event, the start date of the hospitalization was considered to calculate the time to event (i.e., the number of days from start of treatment up to the event start date).	52 weeks on average, up to 416 days
Secondary	Time to First Asthma Exacerbation by Exacerbation Category	Time from start of treatment until the first event (asthma exacerbation) or censoring. Patients without the event were considered as censored at the date of last treatment + 1 day. For patients having the event, the start date of the exacerbation was considered to calculate the time to event (i.e., the number of days from start of treatment up to the event start date).; The exacerbation categories were: All (mild, moderate and severe), combination of moderate or severe and severe.	52 weeks on average, up to 416 days
Secondary	Annual Rate of Asthma Exacerbations by Exacerbation Category	The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.	52 weeks
Secondary	Duration in Days of Asthma Exacerbations by Exacerbation Category	The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.	Up to Week 52
Secondary	Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category	The exacerbation categories were: All (mild, moderate and severe) and combination of moderate or severe and severe.	Up to Week 52
Secondary	Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbation	Time from start of treatment until the first event (permanent discontinuation of study medication due to asthma exacerbation) or censoring. Patients without the event were considered as censored at the date of last treatment + 1 day. For patients having the event, the date of the discontinuation of study medication was considered to calculate the time to event.	52 weeks on average, up to 416 days
Secondary	Total Amount of Oral Corticosteroid Used (in Prednisone-equivalent mg Doses) to Treat Asthma Exacerbations	The treatment of asthma exacerbations including the initiation of systemic corticosteroids were done according to investigator's or treating physician's medical judgement and in line with national and international recommendations. If systemic corticosteroids were required, a participant could return to the study after successfully completing a taper of approximately 7-10 days.	Up to Week 52
Secondary	Change From Baseline in Percentage of Rescue Medication Free Days Over 26 and 52 Weeks	All participants were given salbutamol/albuterol to use as rescue medication throughout the study along with e-Diary to record rescue medication use. Rescue medication free days is defined as any day where the participant did not use any puffs of rescue medication during daytime and night-time.	Baseline, 26 weeks, 52 weeks
Secondary	Asthma Quality of Life Questionnaire (AQLQ) at Week 52	AQLQ is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). It consists of 4 domains: Symptoms = Mean of Items 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 29, 30 (12 items); Activity limitation = Mean of Items 1, 2, 3, 4, 5, 11, 19, 25, 28, 31, 32 (11 items); Emotional function = Mean of Items 7, 13, 15, 21, 27 (5 items); Environmental stimuli = Mean of Items 9, 17, 23, 26 (4 items); Overall Score = Mean of Items 1 to 32 (32 items) The overall AQLQ score reported below is the mean of all 32 responses and ranges from 1 to 7, where higher scores indicate better quality of life.	52 weeks
Secondary	Pre-dose FEV1 at Weeks 4 and 12	Pre-dose FEV1 is defined as average of the two FEV1 measurements taken 45 min and 15 min pre evening dose. It was assessed by performing spirometric assessment. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.	4 weeks, 12 weeks
Secondary	Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes	A composite endpoint of serious asthma outcomes is defined as asthma-related hospitalization, asthma-related intubation, or asthma-related death and was reviewed by the Adjudication Committee.	Up to Week 52