Compare the superiority of CHF 1535 versus CHF 718 in subjects with asthma who are on medium or high dose inhaled corticosteroids.
This was a phase III, multicenter, randomized, double-blind active controlled 2-arm parallel group to compare superiority of CHF 1535 pressurised metered dose inhaler (pMDI) compared with CHF 718 pMDI, in subjects with asthma on medium or high dose inhaled corticosteroids, with regard to change from baseline in forced expiratory volume in the first second (FEV1) Area under the Curve Calculated Between Time 0 and 12 Hours (AUC0-12h) at Week 12. After screening, eligible subjects entered a 2-week run-in period using CHF 718 (BDP) pMDI 100µg, followed by a 12-week double-blind, treatment period. Screened subjects who were on a medium dose inhaled corticosteroid (ICS) or medium dose ICS-long-acting β2-adrenergic receptor agonists (LABA) prior to the study, received CHF 718 pMDI 100µg 2 inhalations twice daily (BID) i.e. total daily dose (TDD) 400µg) during the 2-week run in period. Screened subjects who were on a high dose ICS prior to the study received CHF 718 pMDI 100µg 4 inhalations BID (TDD 800µg) during the 2-week run in period. Following the run-in period, eligible subjects were randomized to one of two study drug arms (using a 1:1 allocation ratio) for 12 weeks. A total of 6 clinic visits (V), (V0-V5) and a follow-up call (V6) were performed during the study. During the study, daily symptoms, rescue medication use, and compliance with the study drug were recorded via a subject-specific electronic diary (eDiary). Concomitant medications and adverse events (AEs) were assessed and recorded throughout the study. Vital signs measurements, physical exam, 12-lead electrocardiogram (ECG), peak expiratory flow (PEF), and spirometry measurements, including serial spirometry were performed and recorded. Symptoms were assessed using disease specific questionnaires. Routine hematology, blood chemistry, and urine pregnancy testing were performed before enrolment and at the end of study. CHF 1535 pMDI = 200/6 μg pressurised metered dose inhaler (fixed combination of extrafine beclomethasone dipropionate \[BDP\] plus formoterol fumarate \[FF\]). CHF 718 pMDI = 100 μg pressurised metered dose inhaler (extrafine beclomethasone dipropionate \[BDP\]).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,377
Available in pressurized inhalation solution BDP/FF 200/6 µg
Available in pressurized inhalation solution BDP 100 µg
1_Change From Baseline in FEV1 AUC0-12h Normalised by Time at Week 12
The pre-dose FEV1 at baseline (i.e. pre-dose on Week 0 \[Visit 2\]) and the FEV1 AUC0-12h normalised by time at Week 12 (Visit 5) are presented by treatment group in the ITT population, as change from baseline. AUC0=12h Area under the curve calculated between time 0 and 12 hours
Time frame: Baseline (pre-dose on Week 0) and Week 12.
2_Change From Baseline in Peak FEV1 Within the First 3 Hours Post-dose at Week 12
The peak FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the peak FEV1 within the first 3 hours post-dose at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline. FEV1=Forced Expiratory Volume in the First Second
Time frame: Baseline (pre-dose on Week 0) and Week 12.
3_Change From Baseline in FEV1 AUC0-12h Normalised by Time at Week 0
The pre-dose FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the FEV1 AUC0-12h normalised by time at Week 0 (V2, post-dose) are presented by treatment group in the ITT population, as change from baseline.
Time frame: Baseline (pre-dose on Week 0) and Week 12.
4_Change From Baseline in Peak FEV1 Within the First 3 Hours Post-dose at Week 0
The peak FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the peak FEV1 within the first 3 hours post-dose at Week 0 (V2, post-dose) are presented by treatment group in the ITT population, as change from baseline. FEV1=Forced Expiratory Volume in the First Second
Time frame: Baseline (pre-dose on Week 0) and 3 h post dose on Week 0.
5_Change From Baseline in Trough FEV1 at Week 12
The trough FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]), the trough FEV1 at Week 12 (V5) and the change from baseline in trough FEV1 at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline. FEV1=Forced Expiratory Volume in the First Second
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Chiesi Clinical Trial Site 840858
Mobile, Alabama, United States
Chiesi Clinical Trial Site 840895
Chandler, Arizona, United States
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Encinitas, California, United States
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Huntington Beach, California, United States
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Huntington Beach, California, United States
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Long Beach, California, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
Chiesi Clinical Trial Site 840869
Newport Beach, California, United States
Chiesi Clinical Trial Site 840890
North Hollywood, California, United States
...and 81 more locations
Time frame: Baseline (pre-dose on Week 0) and Week 12.
6_Change From Baseline in Pre-dose Morning FEV1 at Weeks 4, 8 and 12
The pre-dose MORNING FEV1 at baseline (i.e. pre-dose on Week 0 \[V2\]) and the pre-dose morning FEV1 at Week 4 (V3), Week 8 (V4) and Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline. FEV1=Forced Expiratory Volume in the First Second
Time frame: Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.
7_Proportion of Pre-dose Morning FEV1 Responders at Weeks 4, 8 and 12
The proportion of pre-dose MORNING FEV1 responders at Week 4 (V3), Week 8 (V4) and Week 12 (V5) are presented by treatment group in the ITT population. The proportion of subjects classified as pre-dose morning FEV1 responders (i.e. those subjects who had change from baseline in pre-dose morning FEV1 ≥100 mL). FEV1=Forced Expiratory Volume in the First Second
Time frame: Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.
8_Proportion of Trough FEV1 Responders at Week 12
The proportion of trough FEV1 responders at Week 12 (V5) are presented by treatment group in the ITT population. The proportion of subjects classified as trough FEV1 responders (i.e. those subjects who had change from baseline in trough FEV1 ≥100 mL). FEV1=Forced Expiratory Volume in the First Second
Time frame: Baseline (pre-dose on Week 0) and Week 4, Week 8, Week 12.
9_Change From Baseline in Average Morning Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period
The average MORNING PEF at baseline (i.e. average morning "Best PEF" values during the run-in period, over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population), as change from baseline. PEF=Peak Expiratory Flow
Time frame: Baseline (Week 0) to Week 12.
10_Change From Baseline in Average Evening Peak Expiratory Flow (PEF) Over the 12-Week Treatment Period
The average EVENING PEF at baseline (i.e. average evening "Best PEF" values during the run-in period, see Section 9.7.1.4), over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline. PEF=Peak Expiratory Flow
Time frame: Baseline (Week 0) to Week 12.
11_Change From Baseline in ACQ-7 Score and ACQ-5 Score at Week 12
The ACQ-7 and ACQ-5 scores at baseline (i.e. pre-dose on Week 0 \[V2\]) and at Week 12 (V5) are presented by treatment group in the ITT population, as change from baseline; only patients who provided required data at baseline and at specified times are included in the calculation. Asthma control was evaluated during the treatment period (Week 0 to Week 12 \[V2-V5\])/end of treatment (ET) if applicable, using ACQ-7; first 6 items refer to symptoms and rescue use in the previous 7 days. The 7th item, filled in by the clinical staff, was the FEV1 (% predicted) recorded at 15 min pre-dose, measured at each visit during the treatment period. ACQ-5 has 5 items on adequacy of asthma control. ACQ-7: Assess asthma symptoms over last 7 days (night-time awakenings due to symptoms, morning symptoms, activity limitation, shortness of breath, wheezing), average daily rescue medication use, and current FEV1 percent predicted. Score scale: 0=totally controlled; 6=severely uncontrolled.
Time frame: Baseline (pre-dose on Week 0) and Week 12.
12_Change From Baseline in Percentage of Rescue Medication-free Days Over the 12-Week Treatment Period
The percentage of rescue medication-free days at baseline (i.e. percentage of days during the run-in period with no rescue medication), over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline.
Time frame: Baseline (pre-dose on Week 0) and Week 12.
13_Change From Baseline in Percentage of Asthma Symptom-free Days Over the 12-Week Treatment Period
The percentage of asthma symptom-free days at baseline (i.e. percentage of days during the run-in period with no asthma symptom, over each inter-visit period and over the 12-week treatment period are presented by treatment group in the ITT population, as change from baseline.
Time frame: Baseline (pre-dose on Week 0) and Week 12.