Trial Outcomes & Findings for Foster 100/6 mg NEXThaler Versus Foster 100/6mg Pressurized Metered-dose Inhaler (pMDI) in Patients With Controlled Asthma. (NCT NCT03453112)

The trial began Oct 2017 and completed in Dec 2021, including the period COVID19 pandemic occurred in China. Enrollment in the 46 active sites was paused from Feb 2020, resuming from March 2020 in 8 sites and by 15 June 2020 in 38 sites. Of the patients screened, 494 entered a 4-week run-in period (V1, week -4) and afterward were enrolled and randomized (V3, week 0) into the two treatment groups: * Foster® NEXThaler® 100/6 µg Arm (n=252) * Foster® pMDI 100/6 µg Arm (n=242)

Before randomization, all 494 patients underwent a 4-week open-label run-in phase with Foster® pMDI 100/6 µg (beclometasone dipropionate/formoterol fumarate, two puffs b.i.d.) to standardize baseline therapy. This phase assessed adherence, inhaler technique, spirometry, rescue medication use, and safety parameters. Patients who completed the run-in phase and met eligibility criteria were randomized 1:1 into one of the two treatment arms.

Foster 100/6 mg NEXThaler Versus Foster 100/6mg Pressurized Metered-dose Inhaler (pMDI) in Patients With Controlled Asthma.

PEF= peak expiratory flow. The peak expiratory flow (also known as a peak flow or peak flow rate) is the maximal rate that a person can exhale during a short maximal expiratory effort after a full inspiration. In this study PEF (L/min) was monitored twice daily using a portable electronic peak flow meter before medication intake: morning (7:00-9:00 am) and evening (7:00-9:00 pm). Each session required at least two blows, with the highest valid value recorded. * Baseline pre-dose morning PEF was calculated as the mean of all valid pre-dose morning Best PEF values from the last 14 days before randomization (Week 0, Visit 3). * The average pre-dose morning PEF over the entire treatment period was computed as: ∑Valid pre-dose morning Best PEF values (treatment period) / Number of days with available data * Valid pre-dose morning Best PEF values = Highest value recorded from at least two PEF measurements per session, within the range 50-900 L/min

PEF (L/min) was monitored twice daily using a portable electronic peak flow meter before medication intake: in the morning (7:00-9:00 am) and evening (7:00-9:00 pm). Each session required at least two blows, with the highest valid value recorded. * Baseline pre-dose morning PEF was calculated as the mean of all valid pre-dose morning Best PEF values from the last 14 days before randomization (Week 0, Visit 3). * The average pre-dose morning PEF for each inter-visit period was computed as: ∑all valid pre-dose morning Best PEF values / number of days with available data * Valid pre-dose morning Best PEF values = Highest value recorded from at least two PEF measurements per session, within the range 50-900 L/min

PEF (L/min) was monitored twice daily using a portable electronic peak flow meter before medication intake: morning (7:00-9:00 am) and evening (7:00-9:00 pm). Each session required at least two blows, with the highest valid value recorded. * Baseline pre-dose evening PEF was calculated as the mean of all valid pre-dose evening Best PEF values from the last 14 days before randomization (Week 0, Visit 3). * The average pre-dose evening PEF for each inter-visit period was computed as: ∑all valid pre-dose evening Best PEF values / number of days with available data * Valid pre-dose evening Best PEF values = Highest value recorded from at least two PEF measurements per session, within the range 50-900 L/min.

PEF (L/min) was monitored twice daily using a portable electronic peak flow meter before medication intake: morning (7:00-9:00 am) and evening (7:00-9:00 pm). Each session required at least two blows, with the highest valid value recorded. * Baseline average daily PEF variability was calculated as the mean of all daily PEF variability values recorded in the last 14 days before randomization (Week 0, Visit 3). * The average daily PEF variability for each inter-visit period was computed as: ∑all daily PEF variability values / number of days with available data * Daily PEF variability was calculated only for days where both pre-dose morning Best PEF and pre-dose evening Best PEF values were available. * Valid Best PEF values were defined as the highest value recorded from at least two PEF measurements per session, within the range 50-900 L/min.

Rescue medication use was recorded daily in an electronic diary, with puffs taken during the day recorded in the evening session and puffs taken at night recorded the next morning. * Baseline rescue medication use was the mean daily use over the last 14 days before randomization (Week 0, Visit 3). * Average daily use of rescue medication was calculated as: * all puffs per day / number of days with available data * It was assessed for each inter-visit period (from the evening of the clinic visit to the morning of the next visit) and over the entire treatment period (from the evening of the first treatment day to the morning of the last). * At least 7 valid days were required per period, with at least one evaluable inter-visit period needed for full analysis.

Rescue medication use was recorded daily in an electronic diary, with puffs taken during the day recorded in the evening session and puffs taken at night recorded the next morning. * Baseline percentage of rescue medication-free days was calculated over the last 14 days before randomization (Week 0, Visit 3). * Percentage of rescue medication-free days was calculated as: (Number of days with no rescue medication use / Total number of days with available data)×100 * It was assessed for each inter-visit period (from the evening of the clinic visit to the morning of the next visit) and over the entire treatment period (from the evening of the first treatment day to the morning of the last). * At least 7 valid days were required per period, with at least one evaluable inter-visit period needed for full analysis.

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: 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 (recorded in the evening session, as per study methodology). 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 average of daytime asthma symptoms is the mean value of all daytime measurements, ranging from 0 (no symptoms) to 12 (maximum severity). The lower the score, the better the symptom.

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 (Recorded in the morning session of the next day). 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 average of nighttime asthma symptoms is the mean value of all nighttime measurements, ranging from 0 (no symptoms) to 12 (maximum severity). The lower the score, the better the symptom.

An asthma symptom-free day was defined as a day with both total morning and total evening asthma symptom scores = 0. Only days with both scores available were included. * Baseline percentage of symptom-free days was the mean percentage over the last 14 days before randomization (Week 0, Visit 3). * Percentage of asthma symptom-free days was calculated as: (Number of symptom-free days / Total number of days with available data)×100 * It was assessed for each inter-visit period (from the evening of the clinic visit to the morning of the next visit) and over the 12-week treatment period (from the evening of treatment start to the morning of treatment end). * At least 7 valid days were required per period, with at least one evaluable inter-visit period needed for full analysis.

An asthma control day was defined as a day without rescue medication use and with both total morning and total evening asthma symptom scores = 0. Only days with both scores available were included in the calculation. * Baseline percentage of asthma control days was the mean percentage over the last 14 days before randomization (Week 0, Visit 3). * Percentage of asthma control days was calculated as: (Number of asthma control days / Total number of days with available data)×100 * It was assessed for each inter-visit period (from the evening of the clinic visit to the morning of the next visit) and over the 12-week treatment period (from the evening of treatment start to the morning of treatment end). * At least 7 valid days were required per period, with at least one evaluable inter-visit period needed for full analysis.

Forced Expiratory Volume in 1 second (FEV1) was measured pre-dose in the morning (7:00-9:00 am) at each clinic visit using spirometry, following standardized procedures. Baseline FEV1 was recorded at Visit 3 (Week 0, randomization), and changes were assessed at each visit (Weeks 2, 4, 6, 8, 10, and 12). Patients performed spirometry in a seated position, using the same calibrated spirometer across all visits. They inhaled deeply to total lung capacity and exhaled forcefully and completely. At least three acceptable maneuvers were required, with the highest valid measurement recorded. FEV1 was expressed in liters (L), and a higher value indicated better lung function.

Forced vital capacity (FVC) is the maximum capacity of air that a patient can exhale after a maximum inspiration. It measures the volume of air exhaled in a spirometer, after a maximal inspiration. FVC was measured pre-dose in the morning (7:00-9:00 am) at each clinic visit using spirometry, following standardized procedures. Baseline FVC was recorded at Visit 3 (Week 0, randomization), and changes were assessed at each visit (Weeks 2, 4, 6, 8, 10, and 12). Patients performed spirometry in a seated position, ensuring consistency across visits. They were instructed to inhale deeply to full lung capacity and exhale forcefully and completely into the spirometer. At least three acceptable maneuvers were required per session, with the highest valid measurement recorded. The higher the capacity, measured in liters, the better the outcome.

The ACQ-6 was a validated questionnaire assessing asthma control, consisting of six items: five on asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing) and one on rescue medication use, all self-administered. Each item was scored from 0 (no impairment) to 6 (maximum impairment), and the ACQ-6 total score was the mean of all six items, ranging from 0 (totally controlled asthma) to 6 (severely uncontrolled asthma). Hence, the higher the score, the worse the outcome. Baseline ACQ-6 was assessed at Visit 3 (Week 0, randomization), and the final score was recorded at Visit 9 (Week 12, EOT). The change from baseline was calculated as the difference between these values .

An adverse event (AE) was defined as "any untoward medical occurrence in a patient or clinical study patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment". An AE could therefore be any unfavourable and unintended sign (including abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An adverse drug reaction (ADR) was defined as an "untoward and unintended response to an investigational medicinal product related to any dose administered". An SAE/serious ADR was defined as any untoward medical occurrence or effect that at any dose Resulted in death, Was life-threatening, Required hospitalisation or prolongation of existing hospitalisation, Resulted in persistent or significant disability or incapacity, Was a congenital anomaly or birth defect, Was a medically significant AE.