A Study to Assess the Effect of QAW039 in Non-atopic Asthmatic Patients

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: QAW039
Drug: Placebo QAW039
Drug: Fluticasone 100 mcg
Drug: Fluticasone 250 mcg

Registration Number: NCT01836471

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 345

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Atopic	Fluticasone 100 mcg	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
QAW039 450 mg qd Non-atopic	QAW039	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.
Fluticasone 150 mcg bid Atopic	Fluticasone 250 mcg	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
QAW039 450 mg qd Non-atopic	Fluticasone 100 mcg	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.
Placebo Non-atopic	Fluticasone 100 mcg	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.
QAW039 450 mg qd Atopic	Fluticasone 100 mcg	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
Placebo Non-atopic	Placebo QAW039	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.
Fluticasone 150 mcg bid Atopic	Placebo QAW039	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
Placebo Atopic	Placebo QAW039	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
QAW039 450 mg qd Atopic	QAW039	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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Trough FEV1 (L) in Non-atopic Patients at Week 12 - Full Analysis Set	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 Outcome Measures

Name	Time	Method
Change From Baseline in Trough FEV1 (L) in Atopic Patients at Week 12 - Full Analysis Set	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 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.
Change From Baseline in Trough FEV1 (L) in Non-atopic Compared to Atopic Patients at Week 12 - Full Analysis Set	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 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, 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.
Change From Baseline in ACQ-6 Score at Week 12 Non-atopic and Atopic Patients at Week 12 - Full Analysis Set	baseline,12 weeks	ACQ-6 consists of:5 items on symptoms, 1 item on rescue bronchodilator use, and 1 item on airway caliber (FEV1 % predicted). The ACQ was fully validated, including a minimal important difference (MID) or smallest change that could be considered clinically important (0.5). The ACQ was self-administered at the clinic and patients scored each item on a 7-point response scale: 0 = 'totally controlled' and 6 = 'severely uncontrolled.' Study staff scored question 7 based on % predicted FEV1 (ideally pre-bronchodilator). The total score=average of first 6 questions. Baseline=the ACQ-6 measurement taken prior to first dose of randomized study drug. The single missing score was interpolated by utilizing prior or subsequent completions of the questionnaire. Estimates were from a mixed effects model with treatment, subject population (non-atopic vs. atopic), treatment by subject population interaction, baseline ACQ-6 and region as fixed effects and center nested within region as random effects.
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	ACQ-6 consists of:5 items on symptoms, 1 item on rescue bronchodilator use, and 1 item on airway caliber (FEV1 % predicted). The ACQ was fully validated, including a minimal important difference (MID) or smallest change that could be considered clinically important (0.5). The ACQ was self-administered at the clinic and patients scored each item on a 7-point response scale: 0 = 'totally controlled' and 6 = 'severely uncontrolled.' Study staff scored question 7 based on % predicted FEV1 (ideally pre-bronchodilator). The total score=average of first 6 questions. Baseline=the ACQ-6 measurement taken prior to first dose of randomized study drug. The single missing score was interpolated by utilizing prior or subsequent completions of the questionnaire. Estimates were from a mixed effects model with treatment, subject population (non-atopic vs. atopic), treatment by subject population interaction, baseline ACQ-6 and region as fixed effects and center nested within region as random effects.