Trial Outcomes & Findings for Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients (NCT NCT01577082)

Recruitment occurred across 57 centers in 9 countries, where 542 patients were screened, and 376 were randomized to CHF 1535 (192) or BDP HFA (184). Pre-screening assessed patient eligibility, followed by a screening phase that included medical history review, spirometry, and confirmation of inclusion/exclusion criteria.

After enrollment, participants entered a 2-week open-label run-in phase with beclomethasone dipropionate (BDP) pMDI at 800 µg/day (4 puffs morning/evening). During this phase, compliance, lung function, and asthma control were monitored. At Visit 2 (Week 0), eligible patients were randomized into two treatment groups for the 12-week double-blind phase.

Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients

PEF is a key indicator of lung function, measuring the maximum speed of air exhaled during a forceful breath. Patients used an electronic peak flow meter (Vitalograph®) to record morning pre-dose PEF values daily, with data transmitted to an e-diary. Baseline PEF, measured during the 2-week run-in period, served as a reference for post-treatment changes. To ensure accuracy, PEF was measured before taking the study medication, following a standardized procedure. Patients inhaled deeply to total lung capacity and exhaled forcefully into the device, with the highest value from three maneuvers recorded. The device provided real-time feedback, prompting a repeat if errors occurred, such as delayed effort (\>120 msec), coughing, or inconsistent results (\>40 L/min variation). Higher PEF values indicate better lung function, while a decline suggests worsening obstruction.

PEF is a key indicator of lung function, measuring the maximum speed of air exhaled during a forceful breath. In the FORCE study, patients recorded morning pre-dose PEF values daily using an electronic peak flow meter (Vitalograph®), with data automatically transmitted to an e-diary. Baseline PEF, measured during the 2-week run-in period, served as a reference for assessing lung function changes at each inter-visit period. To ensure accuracy, PEF was measured before taking the study medication, following a standardized protocol. Patients inhaled deeply to total lung capacity and exhaled forcefully, with the highest value from three acceptable maneuvers recorded. The device provided real-time feedback, prompting retests if errors were detected, such as delayed effort (\>120 msec), coughing, or inconsistent results (\>40 L/min variation). Higher PEF values indicated improved lung function, while a decline suggested worsening airflow obstruction.

PEF (Peak Expiratory Flow) was measured at home by patients using a portable electronic peak flow meter. Patients were instructed on the purpose and proper technique for PEF measurement, and detailed usage guidelines were provided. During the run-in and throughout the treatment period, PEF was monitored twice daily-once in the morning and once in the evening-prior to taking the background or study medication. PEF measurements were also recorded during study visits for informational purposes. Each measurement session consisted of three consecutive blows, with the highest value being stored in the device. The average pre-dose evening PEF was calculated as the mean of all available evening PEF measurements within a given period. If fewer than 20 valid measurements were recorded during a specific period, the average value was set as missing.

PEF (Peak Expiratory Flow) was measured at home using a portable electronic peak flow meter. Patients were instructed on proper measurement techniques, and detailed usage guidelines were provided. During the run-in and treatment periods, PEF was recorded twice daily (morning and evening) before taking the background or study medication. Each session consisted of three blows, with the highest value stored. Daily PEF variability was calculated as: Daily PEF variability=(Best morning PEF-Best evening PEF) / (Mean of best morning and evening PEF)×100 The average daily PEF variability for each inter-visit period and the entire treatment period was the mean of all available daily values. If fewer than 20 valid daily values were recorded, the average was set as missing.

The average daily use of rescue medication was assessed at each inter-visit period and over the entire 12-week treatment period. Patients recorded the number of puffs of short-acting β2-agonists (SABA) per day using an electronic diary, ensuring accurate data collection. A decrease in rescue medication use indicated improved asthma control, while an increase suggested worsening symptoms.

The percentage of rescue use-free days indicates asthma control by measuring days when no short-acting β2-agonist (SABA) was used. In this study, the proportion of days without rescue medication use was assessed at each inter-visit period and over the entire 12-week treatment period, with baseline values from the 2-week run-in period as a reference. Patients recorded daily SABA use in an electronic diary, ensuring accurate tracking. An increase in rescue use-free days reflected improved asthma control, while a decrease suggested greater symptom burden.

Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Daytime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 No symptom 1. Mild: aware of symptoms which can be easily tolerated 2. Moderate: discomfort causing interference with daily activity 3. Severe: inability to work/make usual activity The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score daytime = Σ〖Cough daytime score + Wheeze daytime score + Chest Tightness daytime score + Breathlessness daytime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity) where the lower the overall score daytime, the better the outcome. A lower score indicates better symptom control.

Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Nighttime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 No symptom 1. Mild: symptoms not causing awakening 2. Moderate: discomfort causing awakenings 3. Severe: causing awakenings for most of the night / don't allow to sleep at all The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score nighttime = Σ〖Cough nighttime score + Wheeze nighttime score + Chest Tightness nighttime score + Breathlessness nighttime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity), where the lower the overall score nighttime, the better the outcome. A lower score indicates better symptom control.

The percentage of asthma symptom-free days measures the proportion of days when patients reported no daytime or nighttime asthma symptoms, reflecting overall disease control. In this study, it was assessed at each inter-visit period and over the entire 12-week treatment period. Patients recorded symptoms daily in an electronic diary, using a 4-point scale for both daytime (shortness of breath, wheezing, chest tightness, activity limitation) and nighttime (sleep disturbances due to asthma) symptoms. A symptom-free day was defined as a day with a score of 0 for both daytime and nighttime symptoms. An increase in symptom-free days indicated better asthma control, while a decrease suggested worsening disease burden.

The percentage of asthma symptom-free days represents the proportion of days when patients experienced no asthma symptoms, providing a measure of disease control. This outcome was evaluated at each inter-visit period and over the entire 12-week treatment period. Patients recorded daily symptoms in an electronic diary, using a 4-point scale for both daytime (0 = no symptoms, 3 = severe symptoms limiting activity) and nighttime (0 = no symptoms, 3 = symptoms severely affecting sleep) asthma symptoms. A symptom-free day was defined as a day when both daytime and nighttime symptom scores were 0. An increase in symptom-free days indicated better asthma control, while a decrease suggested worsening symptom burden.

Forced Expiratory Volume in 1 second (FEV1) is a key lung function measure, quantifying the volume of air forcefully exhaled in the first second of a forced expiratory maneuver. In this study, spirometry was conducted at baseline and at scheduled visits over a 12-week period to assess the effects of CHF 1535 pMDI versus BDP HFA pMDI (Qvar®) in patients with uncontrolled asthma on high-dose ICS or medium-dose ICS+LABA. Baseline FEV1, recorded at the end of the 2-week run-in phase, served as a reference for post-treatment changes. Tests were performed under controlled conditions using calibrated spirometers, ensuring precision. Patients inhaled deeply to full capacity and exhaled forcefully into the device, completing at least three acceptable maneuvers, with the highest value recorded for analysis. FEV1 is measured in liters (L), where higher values indicate better lung function. Improvements reflect enhanced airway patency, while a decline suggests worsening obstruction.

Forced Vital Capacity (FVC) measures the total volume of air exhaled forcefully after a deep breath, providing key insights into lung function. In this study, pre-dose morning FVC was assessed at each clinic visit and over the entire treatment period. Baseline values were recorded at the end of the 2-week run-in period and used as a reference. Spirometry was conducted before study medication intake under standardized conditions using calibrated devices. Patients inhaled deeply to full lung capacity and exhaled forcefully until no air remained, with the highest value from three acceptable maneuvers recorded. Real-time feedback ensured test accuracy, prompting retests if needed. Higher FVC values indicated improved lung function, while lower values suggested airflow limitation.

The Asthma Control Questionnaire (ACQ) assessed asthma control using a 7-item scale, where each item was scored from 0 (no impairment) to 6 (severe impairment). The total score was the average of all items, ranging from 0 (well-controlled asthma) to 6 (poorly controlled asthma). The scale included five symptom-related questions on nighttime awakenings, activity limitation, shortness of breath, wheezing, and morning symptoms, along with one question on rescue medication use and one on lung function. Patients completed the questionnaire at clinic visits, reporting symptom frequency and impact on daily activities. A decrease in ACQ score reflected improved asthma control, with a reduction of ≥0.5 points considered clinically meaningful.

Asthma exacerbations were defined as worsening respiratory symptoms requiring increased medication use or medical intervention. Moderate exacerbations included increased use of rescue medication, temporary oral corticosteroid use, or unscheduled medical visits. Severe exacerbations were episodes requiring hospitalization, emergency room visits, or prolonged corticosteroid treatment. The number of exacerbations per patient was recorded to evaluate the impact of treatment on asthma stability and disease progression.

An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". A SAE is defined as any untoward medical occurrence or effect that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. An ADR is defined as An Adverse Drug Reaction (ADR) is defined as a harmful or unintended response to a medicinal product at normal doses used for prevention, diagnosis, or treatment. ADRs are considered causally related to the drug and can range from mild to severe, including serious outcomes such as hospitalization or life-threatening conditions.