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

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2016/06/007062
• Date of registration: 30-06-2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Healthcare Private Limited
• 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, Parallel group, Active Controlled Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma - NA
• Date of first enrolment: 30-06-2016
• Target sample size: 3155
• Recruitment status: Closed to Recruitment of Participants
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=14511
• Study type: Interventional
• Study design: Randomized, Parallel Group, Active Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator and Outcome Assessor Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Jordan, Latvia, Lebanon, Lithuania, Luxembourg, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, United Arab Emirates, United Kingdom, Viet Nam

Contacts

• Name: Murugananthan K
• Affiliation: Novartis Healthcare Private Limited

• Name: Murugananthan K
• Affiliation: Novartis Healthcare Private Limited

Key inclusion & exclusion criteria

Inclusion criteria: • Patients with a diagnosis of asthma, (GINA 2015 >= step 4) for a period of at least 1 year prior to Visit 1 (Screening).

• Patients who have used ICS/LABA combinations (Appendix 10) for asthma for at least 1 year 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 >= 2 at Visit 1 (or 101 if no wash-out required) and at Visit 102 (randomization visit) (GINA 2015>= step 4).

• 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 after withholding bronchodilators at both visits 101 and 102.

• Withholding period of bronchodilators prior to spirometry: SABA for >= 6 hrs, LABA (or FDC of ICS/LABA) for >= 24 hrs (48 hrs for indacaterol FDC), SAMA for >= 8 hrsxanthines >= 7 days.

• Retesting is allowed once only. Re-assessment of percentage predicted FEV1 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. Spacer devices are not permitted during reversibility testing.

• 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 may 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 1 year 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) and historical evidence of reversibility is not available (or was not performed according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines patients must be screen failed


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, like glaucoma, cataract and fragility fractures, who are according to Investigator medical opinion at risk participating in the study.

• Patients treated with a LAMA for asthma within 12 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 according to the 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 diabetes 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 101) and end of run-in (Visit 102) visits with a resting ventri

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Asthma

Intervention(s)

Intervention1: QVM149 150/50/160µg once daily: QVM149 150/50/160 µg
Dose frequency: Once Daily.
Duration: 52 weeks
Route of administration: Inhalation, delivered via Concept1 device.
Intervention2: QVM149 150/50/80µg once daily: QVM149 150/50/80 µg
Dose frequency: Once Daily. Duration: 52 weeks.
Route of administration: Inhalation, delivered via Concept1 device.
Control Intervention1: QMF149 150/160µg once daily: QMF149 150/160 µg
Dose frequency: Once Daily. Duration: 52 weeks.
Route of administration: Inhalation, delivered via Concept1 device.
Control Intervention2: QMF149 150/320 µg once daily: QMF149 150/320 µg
Dose frequency: Once Daily. Duration: 52 weeks.
Route of administration: Inhalation, delivered via Concept1 device.
Control Intervention3: Salmeterol xinafoate/ fluticasone propionate 50/500 µg, Twice daily: Salmeterol xinafoate/ fluticasone propionate 50/500 µg.
Dose frequency: Twice Daily (b.i.d.).
Duration: 52 weeks.
Route of administration: Inhalation, delivered via delivered via Accuhaler®.

Primary Outcome(s)

Trough FEV1

[ Designated as safety issue: No ]

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 on through FEV1 over 26 weeks of treatment.Timepoint: 26 weeks

Secondary Outcome(s)

â?¢Serious asthma outcome incidence and CCV events/atrial fibrilaltionTimepoint: 52 weeks

â?¢% rescue medication free days over 26 and 52 weeksTimepoint: 52 weeks

â?¢asthma exacerbation over 52 weeksTimepoint: 52 weeks

� Asthma control as assessed by the Asthma Control Questionnaire (ACQ-7) comparison with salmeterol xinafoate /fluticasone propionate 50/500 µg via Accuhaler®Timepoint: 26 weeks

â?¢% patients with MID ACQ greater than or equals to 0,5 at week 26 and 52Timepoint: 52 weeks

â?¢Adverse events, vital signs, laboratory analysis and ECGTimepoint: 52 weeks

â?¢FEV1 at week 4 and week 12Timepoint: 12 weeks

â?¢Trough FEV1 at week 52Timepoint: 52 weeks

â?¢% days with no symptoms (overall, at awakening and rising)Timepoint: 52 weeks

â?¢AQLQTimepoint: 52 weeks

â?¢% days without rescue medication use over 26 and 52 weeksTimepoint: 52 weeks

â?¢ACQ-7Timepoint: 52 weeks

� Trough FEV1 at 26 weeks comparison with salmeterol xinafoate /fluticasone propionate 50/500 µg via Accuhaler®

Timepoint: 26 weeks

â?¢FVC at week 4 and week 12Timepoint: 12 weeks

â?¢PEF over 26 and 52 weeksTimepoint: 52 weeks

Secondary ID(s)

CQVM149B2302 v03 (clean version) dated 08-Oct-2015

NCT02571777

Source(s) of Monetary Support

Novartis Pharma AG, Basel, Switzerland

Ethics review

Status: Approved
Approval date: 04/03/2016
Contact:

Institutional Ethics Committee Malpani Multispeciality Hospital_Dr Sanjay Khator

Status: Approved
Approval date: 05/03/2016
Contact:

Eternal Heart Care Centre & Research Institute â?? Institutional Ethics Committee_Dr Krishna Kumar Sharma

Status: Approved
Approval date: 09/03/2016
Contact:

Institutional Ethics Committee, Sterling Hospital, Dr Tushar Patel

Status: Approved
Approval date: 18/03/2016
Contact:

Lalitha Super Specialities Hospital Ethics Committee_Dr Lakshmi Kumari

Status: Approved
Approval date: 04/04/2016
Contact:

Ethics Committee, Asthma Bhawan, Dr Ashish Kumar Malpani

Status: Approved
Approval date: 05/04/2016
Contact:

Institutional Ethics Committee - KVM Hospital_Dr Sailal M

Status: Approved
Approval date: 05/04/2016
Contact:

Manipal University Ethics Committee, Kasturba Hospital, Kasturba Medical College Hospital, Dr Vishak Acharya

Status: Approved
Approval date: 11/04/2016
Contact:

Pentamed Ethics Committee_Dr Ashish Goyal

Status: Approved
Approval date: 23/04/2016
Contact:

Institutional Ethics Committee - Global Hospitals & Health City_Dr Vijil Rahulan

Status: Approved
Approval date: 16/05/2016
Contact:

Institutional Ethics Committee, Global Hospitals, Dr Tapaswi Krishna

Status: Approved
Approval date: 19/05/2016
Contact:

Institutional Ethics Committee, Government Medical College, Institute of Chest Diseases, Dr K P Suraj

Status: Approved
Approval date: 20/05/2016
Contact:

Meditrina Institute Ethics Commitee, Meditrina Institute of Medical Science, Dr Vivek Gupta

Status: Approved
Approval date: 25/05/2016
Contact:

Ethics Committee Silver, Research office Christian Medical College, Dr Christopher Devasahayam Jesudas

Status: Approved
Approval date: 15/06/2016
Contact:

Institutional Ethics Committee, Raja Rajeshwari Medical College & Hospital, Dr Mohan Kotnur Rao

Status: Approved
Approval date: 23/06/2016
Contact:

Ethics Committee, St.Theresas Hospital, Dr Nagaraju B

Status: Approved
Approval date: 30/06/2016
Contact:

Bhakti Vedanta Hospital Ethics Committee_Dr Ajay Godse

Status: Approved
Approval date: 04/07/2016
Contact:

Institutional Ethics Committee, Fortis Hospital, Dr Raja Dhar

Status: Approved
Approval date: 05/07/2016
Contact:

Institutional Ethics Commiittee, King George Hospital, Dr Siddhanathi Narasinga Rao

Status: Approved
Approval date: 06/07/2016
Contact:

Ethics Committee, GSVM Medical College_Dr Anand Kumar

Status: Approved
Approval date: 12/07/2016
Contact:

Institutional Ethics Committee, NKP Salve Institute of Sciences & Lata Mangeshkar Hospital, Dr Anil Kishanrao Sontakke

Status: Approved
Approval date: 13/07/2016
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Institutional Ethics Committee - The Madras Medical Mission_Dr Supraja Kalyanaraman

Status: Approved
Approval date: 15/07/2016
Contact:

Institutional Ethics Commiitee -BGS Global Hospital, Dr Vishwanath Bellad

Status: Approved
Approval date: 15/07/2016
Contact:

Institutional Ethics Commiittee, KIMS, Hubli, Dr Ram Kaulgud

Status: Approved
Approval date: 18/07/2016
Contact:

Ethics Committee - Meenakshi Mission Hospital & Research Centre_Dr Velkumar Gopal

Status: Approved
Approval date: 21/07/2016
Contact:

Sri Balaji Action Medical Institute ethics Committee_Dr Animesh Arya

Status: Approved
Approval date: 28/07/2016
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Ethics Committee, S. P. Medical & A.G.Hospital, Dr Surendra Kumar

Status: Approved
Approval date: 02/08/2016
Contact:

Institutional Ethics Committee, SAL Hospital & Medical Institute_Dr Janak Bhavsar

Status: Approved
Approval date: 09/08/2016
Contact:

Institutional Ethics committee Mysore Medical College and Research Institute_Dr Rangaswamy

Status: Approved
Approval date: 11/08/2016
Contact:

Sri Bala Medical Center & Hospital,Institutional Human Ethics Committee_Dr Srikanth Krishnamurthy

Status: Approved
Approval date: 20/08/2016
Contact:

Institutional Ethics Committee, Deccan College and Medical Science and Allied Hospital, Owaisi Hospital and Research Centre, Dr Ashfaq Hasan

Status: Approved
Approval date: 30/08/2016
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Institutional Ethics Commiitee, B J Medical College and Civil Hospital_Dr Bhagirath Solanki

Status: Approved
Approval date: 02/09/2016
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Institutional Ethics committee, BJ Medical College & Sassoon General Hospital, Dr Sushant Meshram

Status: Approved
Approval date: 06/09/2016
Contact:

Sir Ganga Ram Hospital Ethics Committee,Dr UjjwalParakh

Status: Approved
Approval date: 19/09/2016
Contact:

Institutional Ethics Committee, Shri Guru Ram Rai Institute of Medical & Health Sciences, Dr Jagdish Rawat

Status: Approved
Approval date: 28/09/2016
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Ethics Committee, Bioethical Committee, J N Medical College_Dr Zuber Ahmad

Status: Approved
Approval date: 28/09/2016
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Institutional Ethics Committee, Paras Hospital, Dr Arunesh Kumar

Status: Approved
Approval date: 18/10/2016
Contact:

Ethics Committee, Datta Meghe Institute of Medical Sciences(DU), Dr Babaji Ghewade

Status: Approved
Approval date: 30/11/2016
Contact:

Institutional Human Ethics Commiittee, KIMS, Dr Kesavan Nair Veerendran Nair

Status: Approved
Approval date: 05/12/2016
Contact:

Ethics Committee, Siddhartha Medical college & Government General hospital, Dr Suresh Kumar Gattu

Status: Approved
Approval date: 12/12/2016
Contact:

Institutional Ethics Committee - Sree Narayana institute of Medical Sciences_Dr Hemlatha V S

Status: Approved
Approval date: 16/01/2017
Contact:

 Institutional Ethics Committee,I.G.I.M.S,Patna-800014._Dr Manish Shankar

Status: Approved
Approval date: 25/03/2017
Contact:

Institutional Ethics Committee, Fortis Hospital, Dr Amit Kumar Mandal

Status: Approved
Approval date: 25/05/2017
Contact:

Ethics Committee of Manipal Hospitals_Dr Guruprasad Bhat

Status: Approved
Approval date: 06/10/2017
Contact:

Institutional Ethics Committee, Chest Research Foundation, Dr Sundeep Salvi

Status: Approved
Approval date: 09/11/2017
Contact:

Siddhi Hospital Institutional Ethics Comittee, Dr Abhinandan Mutha

Status: Approved
Approval date: 17/01/2018
Contact:

Institutional Ethics Committee, CARE INSTITUTE OF MEDICAL SCIENCES (CIMS), Dr Amit Patel

Status: Not Approved
Approval date:
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Institutional ethics committee for human research, Medical College & Hospital, Dr Raja Bhattacharya

Status: Not Approved
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Institutional Ethics Committee, Institute of Medical Science IMS & SUM Hospital, Dr Banani Jena

Status: Not Approved
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Noble Hospital Institutional Ethics Committee, Noble Hospital Pvt. Ltd. _Dr Rajeev Adkar