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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02571777




Registration number
NCT02571777
Ethics application status
Date submitted
5/10/2015
Date registered
8/10/2015
Date last updated
22/07/2020

Titles & IDs
Public title
Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma
Scientific 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
Secondary ID [1] 0 0
2015-002899-25
Secondary ID [2] 0 0
CQVM149B2302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - QVM149 150/50/160
Treatment: Drugs - QVM149 150/50/80
Treatment: Drugs - QMF149 150/320
Treatment: Drugs - QMF149 150/160
Treatment: Drugs - salmeterol/fluticasone

Experimental: QVM149 150/50/160 µg o.d. - QVM149 150/50/160 µg (indacaterol acetate/glycopyrronium/mometasone furoate) once daily (o.d.) delivered via Concept1 device

Experimental: QVM149 150/50/80 µg o.d. - QVM149 150/50/80 µg (indacaterol acetate/glycopyrronium/mometasone furoate) once daily (o.d.) delivered via Concept1 device

Active Comparator: QMF149 150/320 µg o.d. - QMF149 150/320 µg (indacaterol acetate/mometasone furoate) once daily (o.d.) delivered via Concept1 device

Active Comparator: QMF149 150/160 µg o.d. - QMF149 150/160 µg (indacaterol acetate/mometasone furoate) once daily (o.d.) delivered via Concept1 device

Active Comparator: Salmeterol/fluticasone 50/500 µg b.i.d. - Salmeterol xinafoate /fluticasone propionate 50/500 µg twice daily (b.i.d.) delivered via Accuhaler®


Treatment: Drugs: QVM149 150/50/160


Treatment: Drugs: QVM149 150/50/80


Treatment: Drugs: QMF149 150/320


Treatment: Drugs: QMF149 150/160


Treatment: Drugs: salmeterol/fluticasone


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus QMF149 at Week 26
Timepoint [1] 0 0
26 weeks
Secondary outcome [1] 0 0
Asthma Control Questionnaire (ACQ-7) at Week 26 and Week 52
Timepoint [1] 0 0
26 weeks, 52 weeks
Secondary outcome [2] 0 0
Trough Forced Expiratory Volume in 1 Second (Trough FEV1) of QVM149 Versus Salmeterol/Fluticasone at Week 26
Timepoint [2] 0 0
26 weeks
Secondary outcome [3] 0 0
Trough FEV1 at Week 52
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Pre-dose Forced Vital Capacity (FVC) at Week 4 and Week 12
Timepoint [4] 0 0
4 weeks, 12 weeks
Secondary outcome [5] 0 0
Trough Forced Expiratory Flow (FEF) Between 25% and 75% of FVC (FEF25-75) at 52 Weeks
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEF) Over 26 and 52 Weeks of Treatment
Timepoint [6] 0 0
Baseline, 26 weeks, 52 weeks
Secondary outcome [7] 0 0
Change From Baseline in Percentage of Asthma Symptom-free Days Over 52 Weeks
Timepoint [7] 0 0
Baseline, 52 weeks
Secondary outcome [8] 0 0
Change From Baseline in Percentage of Days With no Daytime Symptoms Over 52 Weeks
Timepoint [8] 0 0
Baseline, 52 weeks
Secondary outcome [9] 0 0
Change From Baseline in Percentage of Nights With no Night-time Awakenings Over 52 Weeks
Timepoint [9] 0 0
Baseline, 52 weeks
Secondary outcome [10] 0 0
Change From Baseline in Percentage of Mornings With no Symptoms on Rising Over 52 Weeks
Timepoint [10] 0 0
Baseline, 52 weeks
Secondary outcome [11] 0 0
Change From Baseline in Percentage of Days Without Rescue Medication Use Over 26 and 52 Weeks
Timepoint [11] 0 0
Baseline, 26 weeks, 52 weeks
Secondary outcome [12] 0 0
Percentage of Patients Achieving the Minimal Clinically Important Difference (MCID) ACQ = 0.5 at Week 26 and Week 52
Timepoint [12] 0 0
26 weeks, 52 weeks
Secondary outcome [13] 0 0
Time to First Hospitalization for Asthma Exacerbation
Timepoint [13] 0 0
52 weeks on average, up to 416 days
Secondary outcome [14] 0 0
Time to First Asthma Exacerbation by Exacerbation Category
Timepoint [14] 0 0
52 weeks on average, up to 416 days
Secondary outcome [15] 0 0
Annual Rate of Asthma Exacerbations by Exacerbation Category
Timepoint [15] 0 0
52 weeks
Secondary outcome [16] 0 0
Duration in Days of Asthma Exacerbations by Exacerbation Category
Timepoint [16] 0 0
Up to Week 52
Secondary outcome [17] 0 0
Percentage of Participants With at Least One Asthma Exacerbation by Exacerbation Category
Timepoint [17] 0 0
Up to Week 52
Secondary outcome [18] 0 0
Time in Days to Permanent Discontinuation of Study Medication Due to Asthma Exacerbation
Timepoint [18] 0 0
52 weeks on average, up to 416 days
Secondary outcome [19] 0 0
Total Amount of Oral Corticosteroid Used (in Prednisone-equivalent mg Doses) to Treat Asthma Exacerbations
Timepoint [19] 0 0
Up to Week 52
Secondary outcome [20] 0 0
Change From Baseline in Percentage of Rescue Medication Free Days Over 26 and 52 Weeks
Timepoint [20] 0 0
Baseline, 26 weeks, 52 weeks
Secondary outcome [21] 0 0
Asthma Quality of Life Questionnaire (AQLQ) at Week 52
Timepoint [21] 0 0
52 weeks
Secondary outcome [22] 0 0
Pre-dose FEV1 at Weeks 4 and 12
Timepoint [22] 0 0
4 weeks, 12 weeks
Secondary outcome [23] 0 0
Percentage of Participants With Composite Endpoint of Serious Asthma Outcomes
Timepoint [23] 0 0
Up to Week 52

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Argentina
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Buenos Aires
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Ruse
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Sofia
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Chile
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Chile
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Santiago
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China
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Petrinja
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Zadar
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Tartu
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NRW
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Sachsen
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Schleswig Holstein
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Annaberg-Buchholz
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Aschaffenburg
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Berlin
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Godollo
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Cork
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Ashkelon
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Israel
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Beer-Sheva
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petach Tikva
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Israel
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Rehovot
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Israel
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Tel Giborim, Holon
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Italy
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BA
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Italy
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CT
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Italy
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CZ
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Italy
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FI
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Italy
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ME
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Italy
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VR
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Italy
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Ancona
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Italy
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Messina
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Pordenone
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Italy
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Roma
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Japan
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Fukuoka
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Japan
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Hokkaido
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Hyogo
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Japan
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Ibaraki
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Japan
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Kanagawa
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Japan
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Mie
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Miyagi
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Shibuya Ku
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Japan
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Shizuoka
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Japan
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Tokyo
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Jordan
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JOR
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Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.