A Double-blind, Placebo-controlled, Study Examining the Effect of Orally Administered QAW039 (450 mg QD) on FEV1 and ACQ in Non-atopic, Asthmatic Patients With a Baseline, Pre-bronchodilator FEV1 of 40-80% Predicted, Inadequately Controlled With Low Dose ICS Therapy
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 345
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Trough FEV1 (L) in Non-atopic Patients at Week 12 - Full Analysis Set
Overview
Brief Summary
The purpose of the study was to assess the clinical effect of QAW039 in non-atopic asthmatics taking low dose Inhaled Corticosteroid (ICS) as background therapy.
Detailed Description
This was a multi-centre, randomised, placebo-controlled, double blind, 3-arm study designed to compare the efficacy and safety of a once daily dose of QAW039 with placebo in non-atopic and atopic asthmatics both inadequately controlled despite receiving a low dose ICS background therapy, over a 12 week treatment period. Efficacy and safety of a once daily dose of QAW039 was also compared with an increased dose of ICS in atopic asthmatics taking low dose ICS as background therapy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent must be obtained before any assessment is performed
- •Patients with a diagnosis of persistent asthma (according to Global Initiative for Asthma 2011) for a period of at least 6 months prior to screening
- •Patients with a pre-bronchodilator Forced Expiratory Volume In One Second (FEV1) value of 40% to 80% of individual predicted value at screening and prior to treatment
- •An Asthma Control Questionnaire score ≥ 1.5 prior to treatment
- •Demonstration of reversible airway obstruction
Exclusion Criteria
- •Pregnant or nursing (lactating) women
- •Acute illness other than asthma at the start of the study
- •Patients with clinically significant laboratory abnormalities at screening
- •Patients with clinically significant condition which may compromise subject safety or interfere with study evaluation
- •Use of other investigational drugs at the time of enrollment
Arms & Interventions
QAW039 450 mg qd Non-atopic
QAW039 450 mg (3 capsules of QAW039 150 mg) qd combined with background ICS (100 μg fluticasone, bid). Non-atopic patients randomized in ratio of approximately 1:1.
Intervention: QAW039 (Drug)
QAW039 450 mg qd Non-atopic
QAW039 450 mg (3 capsules of QAW039 150 mg) qd combined with background ICS (100 μg fluticasone, bid). Non-atopic patients randomized in ratio of approximately 1:1.
Intervention: Fluticasone 100 mcg (Drug)
Placebo Non-atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with background ICS (100 μg fluticasone, bid). Non-atopic randomized in ratio of approximately 1:1.
Intervention: Placebo QAW039 (Drug)
Placebo Non-atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with background ICS (100 μg fluticasone, bid). Non-atopic randomized in ratio of approximately 1:1.
Intervention: Fluticasone 100 mcg (Drug)
QAW039 450 mg qd Atopic
QAW039 450 mg (3 capsules of QAW039 150 mg) qd combined with background ICS (100 μg fluticasone, bid). Atopic patients randomized in a ratio of approximate 1:1:1
Intervention: QAW039 (Drug)
QAW039 450 mg qd Atopic
QAW039 450 mg (3 capsules of QAW039 150 mg) qd combined with background ICS (100 μg fluticasone, bid). Atopic patients randomized in a ratio of approximate 1:1:1
Intervention: Fluticasone 100 mcg (Drug)
Fluticasone 150 mcg bid Atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with 150 μg ICS and with background ICS (100 μg fluticasone, bid). As a consequence total ICS was 250 μg fluticasone bid. Atopic patients randomized in ratio of approximately 1:1:1
Intervention: Placebo QAW039 (Drug)
Fluticasone 150 mcg bid Atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with 150 μg ICS and with background ICS (100 μg fluticasone, bid). As a consequence total ICS was 250 μg fluticasone bid. Atopic patients randomized in ratio of approximately 1:1:1
Intervention: Fluticasone 250 mcg (Drug)
Placebo Atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with background ICS (100 μg fluticasone, bid). Atopic patients andomized in ratio of approximately 1:1:1
Intervention: Placebo QAW039 (Drug)
Placebo Atopic
Placebo to QAW039 (3 capsules of Placebo of QAW039 150 mg) combined with background ICS (100 μg fluticasone, bid). Atopic patients andomized in ratio of approximately 1:1:1
Intervention: Fluticasone 100 mcg (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Trough FEV1 (L) in Non-atopic Patients at Week 12 - Full Analysis Set
Time Frame: baseline,12 weeks
Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline is defined as the last available FEV1 measurement taken prior to the first dose of randomized study drug. Data within 6 hr of rescue medication use is excluded from this analysis. For subjects with missing trough FEV1 (L) at Week 12, the last post baseline observation were used (LOCF). Estimates are from a mixed effects model with treatment, subject population (non-atopic vs. atopic), treatment by subject population interaction, baseline trough FEV1 and region as fixed effects and center nested within region as random effects. Full analysis set included all randomized subjects who received at least one dose of study drug.
Secondary Outcomes
- Change From Baseline in Trough FEV1 (L) in Atopic Patients at Week 12 - Full Analysis Set(baseline,12 weeks)
- Change From Baseline in Trough FEV1 (L) in Non-atopic Compared to Atopic Patients at Week 12 - Full Analysis Set(baseline,12 weeks)
- Change From Baseline in ACQ-6 Score at Week 12 Non-atopic and Atopic Patients at Week 12 - Full Analysis Set(baseline,12 weeks)
- Change From Baseline in ACQ-6 Score at Week 12 Non-atopic Compared to Atopic Patients at Week 12 - Full Analysis Set(baseline,12 weeks)