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
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
Safety and Efficacy study of QVM149 in asthmatic patients
|2010 - 2016||Health Technology Development||Drug Discovery and Development|
|Start Date||Duration in Months||Target Completion Date||Actual Completion Date|
|Novartis Healthcare Philippines, Inc.||Private Business||NCR||CDRR-NCR-S-1|
|Name||Institution and Institution Address|
|Anna Liza Calingasinemail@example.com||Novartis Healthcare Philippines, Inc. 5F Ayala North Exchange Tower 1 Amorsolo corner Salcedo Streets Legaspi Village, Makati City 1229|
|Name||Institution and Institution Address|
|Lawrence Allen Triafirstname.lastname@example.org||Novartis Healthcare Philippines, Inc. 5F Ayala North Exchange Tower 1 Amorsolo corner Salcedo Streets Legaspi Village, Makati City 1229|
|Aileen D. Wang, MD||Pulmonologist||University of the Philippines - Philippine General Hospital|
|Albert B. Albay, Jr., MD||Pulmonologist||Manila Doctors Hospital|
|Araceli Maliwat-Galapon, MD||Pulmonologist||St. Michael Family Hospital|
|Jose Felipe Hernandez, MD||Pulmonologist||Mary Mediatrix Medical Center|
|Joven Roque V. Gonong, MD||Pulmonologist||Lung Center of the Philippines|
|Ma. Bella R. Siasoco, MD||Pulmonologist||St. Luke's Medical Center - Quezon City|
|Project Location||Institutional Ethics Review Board|
|University of the Philippines - Philippine General Hospital||N/A|
|Manila Doctors Hospital||Manila Doctors Hospital Institutional Review Board|
|St. Michael Family Hospital||N/A|
|Mary Mediatrix Medical Center||Mary Mediatrix Medical Center Research Ethics Review Committee|
|Lung Center of the Philippines||Lung Center of the Philippines Ethics Review Committee|
|St. Luke's Medical Center - Quezon City||St. Luke's Medical Center Institutional Ethics Review Board|
The primary objective of this study is 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. all delivered via Concept1 in terms of trough FEV1 after 26 weeks of treatment in patients with asthma.
The key secondary objective is to demonstrate the 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., all delivered via Concept1, in terms of ACQ-7 after 26 weeks of treatment in patients with asthma.
- United Kingdom
Sites randomized 55 patients in the study.
- Male and female adult patient ≥ 18 years old and ≤ 75 years.
- Written informed consent must be obtained before any studyrelated assessment is performed.
- 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 ≥ 1.5 at Visit 101 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. Previous asthma exacerbation in this context is based on patient´s recall of unplanned need for medical care at any primary care physician, pulmonologist, emergency room and/or hospital due to an aggravation of asthma symptoms requiring treatment with systemic corticosteroids due to asthma exacerbation. Every effort should be made by the site to obtain/have appropriate source documentation for these previous asthma exacerbations.
- Pre-bronchodilator FEV1 of < 80 % of the predicted normal value for the patient after withholding bronchodilators (Table 5- 2) at both visits 101 and 102.
- Withholding period of bronchodilators prior to spirometry: SABA for ≥ 6 hrs. LABA (or fixed dose combination of ICS/LABA) for ≥ 24 hrs (48 hrs for indacaterol fixed dose combination (FDC)), SAMA for ≥ 8 hrs, xanthines ≥ 7 days.
- Re-testing 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 ATS/ERS guidelines) patients must be screen failed.
- Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1 (Screening).
- 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 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 definition in Section 6.4.4 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 a history of chronic lung diseases other than asthma, including (but not limited to) COPD, sarcoidosis, interstitial lung disease, cystic fibrosis, clinically significant bronchiectasis and active tuberculosis
- Patients with narcolepsy and/or insomnia
- Patients on Maintenance Immunotherapy (desensitization) for allergies or less than 3 months prior to Visit 101 or patients on Maintenance Immunotherapy for more than 3 months prior to Visit 101 but expected to change throughout the course of the study.
QVM149 and QMF149
The Investigational treatments are as follows:
- QVM149 (indacaterol acetate/ glycopyrronium bromide/MF) 150/50/80 μg o.d. delivered as powder in hard capsules via Concept1
- QVM149 (indacaterol acetate/ glycopyrronium bromide/MF) 150/50/160 μg o.d. delivered as powder in hard capsules via Concept1
The Comparative treatments are:
- QMF149 (indacaterol acetate/MF) 150/160 μg o.d. delivered as powder in hard capsules
- QMF149 (indacaterol acetate/MF) 150/320 μg o.d. delivered as powder in hard capsules
- Salmeterol xinafoate/fluticasone propionate 50/500 μg b.i.d. delivered as powder via
In addition the following placebo will be provided to enable the double-dummy design of the
- Placebo delivered as powder in capsules via Concept1
- Placebo delivered as powder via Accuhaler®
This study uses a 52 week treatment, randomized, double-blind, double-dummy, parallelgroupdesign.
The purpose of the trial is 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.