Trial Outcomes & Findings for Study in Adult Patients With Moderate to Severe Asthma (NCT NCT04886999)

A total of 81 patients were screened. 78 patients were randomized into two treatment sequences: * 39 received Inhaler A first, then Inhaler B. * 39 received Inhaler B first, then Inhaler A.

After signing informed consent, patients underwent screening (V1) for eligibility. Eligible subjects entered a 14-day baseline period receiving all standardized treatment (CHF1535 100/6 µg pMDI) to ensure uniform background therapy. At V2 (Day 15), 78 subjects were randomized (A-B or B-A sequences). 3 patients failed screening, 4 discontinued before randomization, and 74 initiated treatment. Most randomized subjects received at least one dose of study treatment (Inhaler A= 72, Inhaler B = 74).

Study in Adult Patients With Moderate to Severe Asthma

A study-specific questionnaire was developed to evaluate medication use, asthma symptoms, and treatment perception. It consisted of 16 questions, completed by subjects via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). The questionnaire included Visual Analogue Scale (VAS) ratings, numerical responses, and multiple-choice questions, with VAS primarily used to assess symptom perception and psychopharmacological effects. Question #3 (How would you score your asthma symptoms yesterday?) was recorded daily, each morning, from V1 (Day 2) to V4 (Day 43), with subjects rating their asthma symptoms from the previous day on a VAS scale from 0=no symptoms to 100=very symptomatic, with lower scores corresponding to better health. The overall value for each treatment period was defined as the average of the VAS scores collected over the two weeks of treatment within each period. Adjusted means are reported.

A study-specific questionnaire was developed to evaluate medication use, asthma symptoms, and treatment perception. It consisted of 16 questions, completed by subjects via an e-Diary. The questionnaire included Visual Analogue Scale (VAS) ratings, numerical responses, and multiple-choice questions, with VAS primarily used to assess symptom perception and psychopharmacological effects. Question #4 (How burdensome was your asthma yesterday?) was recorded daily, each morning, from V1 (Day 2) to V4 (Day 43), requiring subjects to rate the burden of their asthma symptoms from the previous day on a VAS scale ranging from 0 to 100, where 0=no burden at all and 100=very burdensome. Lower scores corresponded to better health and lower perceived burden of asthma. The overall value for each treatment period was defined as the average of the VAS scores collected over the two weeks of treatment within each period. Adjusted means by treatment are reported with their relative 95% IC.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #5 ("Did your asthma symptoms improve yesterday?") was recorded daily, each morning, from V1 (Day 2) to V4 (Day 43), using a VAS scale from 0 to 100 (0 = no improvement; 100 = maximum improvement), where higher scores indicated better health.The overall value for each treatment period was defined as the average of the VAS scores collected over the two weeks of treatment within each period. Adjusted means are reported with their 95% IC.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #6 ("Did your asthma symptoms worsen yesterday?") was recorded daily, each morning, from V1 (Day 2) to V4 (Day 43), using a VAS scale from 0 to 100 (0 = no worsening; 100 = maximum worsening), where lower scores indicated better health. The overall value for each treatment period was defined as the average of the VAS scores collected over the two weeks of treatment within each period. Adjusted means are reported with their relative 95% IC.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Asthma symptoms were assessed using a VAS, ranging from 0=no symptoms to 100=very severe symptoms. Question #3 (How would you score your asthma symptoms yesterday?) was recorded daily, each morning, from V1 (Day 2) to V4 (Day 43). First week value for each treatment period was defined as the average of the VAS scores that had been collected over the first week of treatment within each period. Change from baseline was calculated as the difference between the average VAS score from baseline (Day 1) and the average VAS score over the first 7 days of treatment. Adjusted means reported with their 95%IC.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Asthma burden was assessed using a Visual Analogue Scale (VAS) ranging from 0=no burden to 100=very burdensome condition. Lower scores corresponded to better health. Question #4 (How burdensome was your asthma yesterday?) was recorded daily in the morning over the first 7 days of treatment. First week value for each treatment period = average of the VAS scores collected over the first week of treatment within each period. Here the change from baseline was calculated as the difference between the average VAS score from baseline (Day 1) and the average VAS score over the first 7 days of treatment.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Asthma symptom improvement was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100, where 0 indicated no improvement at all and 100 indicated maximum improvement. Question #5 ("Did your asthma symptoms improve yesterday?") was recorded daily in the morning over the first 7 days of treatment. First week value for each treatment period was defined as the average of the VAS scores that had been collected over the first week of treatment within each period. The change from baseline was calculated as the difference between the average VAS score. Adjusted means are reported with their 95%IC

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), others only at V2 (Day 15), V3 (Day 29), and V4 (Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Asthma symptom worsening was assessed using a VAS, ranging from 0=no worsening at all to 100= maximum worsening. Question #6 (Did your asthma symptoms worsen yesterday?) was recorded daily in the morning over the first 7 days of treatment. First week value for each treatment period was defined as the average of the VAS scores that had been collected over the first week of treatment within each period. The change from baseline was calculated as the difference between the average VAS score from baseline (Day 1) and the average VAS score over the first 7 days of treatment. Adjusted means are reported.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while psychopharmacological questions were answered only at specific study visit timepoints (two questions at V2-Day 15, four at V3-Day 29, and two at V4-Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #7 (Do you expect any improvement in asthma symptoms with this treatment?) was recorded at V2 (Day 15) and V3 (Day 29), before starting each treatment period. Expected asthma symptom improvement was assessed using a Visual Analogue Scale (VAS) ranging from 0=no expected improvement to 100=maximum expected improvement. Higher scores corresponded to greater expectations of benefit.Summary measures for this question were presented separately as descriptive statistics for the ITT population.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while psychopharmacological questions were answered only at specific study visit timepoints (two questions at V2-Day 15, four at V3-Day 29, and two at V4-Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #8 (Do you expect any worsening of your asthma symptoms with this treatment?) was recorded at V2 (Day 15) and V3 (Day 29), before starting each treatment period. Expected asthma symptom improvement was assessed using a Visual Analogue Scale (VAS) ranging from 0=none to 100=maximum worsening. Lower scores corresponded to better health. Summary measures for this question were presented separately as descriptive statistics for the ITT population.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while psychopharmacological questions were answered only at specific study visit timepoints (two questions at V2-Day 15, four at V3-Day 29, and two at V4-Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #9 ("How much do you think this treatment improved your overall asthma symptoms?") was recorded at V3 (Day 29) and V4 (Day 43), after each treatment period. Perceived improvement in overall asthma symptoms was assessed using a Visual Analogue Scale (VAS) ranging from 0 = none to 100 = maximum improvement. Higher scores corresponded to better health. Summary measures for this question were presented separately as descriptive statistics for the ITT population.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while psychopharmacological questions were answered only at specific study visit timepoints (two questions at V2-Day 15, four at V3-Day 29, and two at V4-Day 43). It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Question #10 ("How much do you think this treatment worsened your overall asthma symptoms?") was recorded at V3 (Day 29) and V4 (Day 43), after each treatment period. Perceived worsening of overall asthma symptoms was assessed using a Visual Analogue Scale (VAS) ranging from 0 = none to 100 = maximum worsening. Lower scores corresponded to better health. Summary measures for this question were presented separately as descriptive statistics for the ITT population.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions was completed via an e-Diary. Questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' visual preference for the inhalers was assessed through Question #11 ("Which inhaler did you visually prefer?"). The question was completed before revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Inhaler A, Inhaler B, or No preference. The number and percentage of subjects selecting one of the three options was summarized separately for the ITT population by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' preference for inhaler use was assessed through Question #12 ("Which inhaler did you prefer to use?"), which was answered only at V4 (Day 43). The question was completed before revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Inhaler A, Inhaler B, or No preference. The number and percentage of subjects selecting one of the three options was summarized separately for the ITT population by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' perception of changes in the inhalers was assessed through Question #13 ("Do you think that changes were made to the inhalers?"), which was answered only at V4 (Day 43). The question was completed before revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Yes, No, or I don't know. The number and percentage of subjects selecting one of the three options was summarized separately for the ITT population by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' perception of the impact of inhaler changes on asthma symptoms was assessed through Question #14 ("Do you think that changes made across the inhalers have impacted your asthma symptoms?"), which was answered only at V4 (Day 43). The question was completed before revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Yes, No, or I don't know. The number and % of subjects selecting one of the options was summarized separately for the ITT population by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' perception of asthma symptoms after receiving information about the inhalers was assessed through Question #15 ("Based on the information you have received, did it impact your perception of your asthma symptoms?"), which was answered only at V4 (Day 43), after revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Yes, No, or I don't know. The number and % of subjects selecting one of the options was summarized separately for the ITT population by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while questions related to device preference and perception were answered only at V4 (Day 43) during the Exit Interview. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Subjects' perception of which inhaler had the biggest impact on their asthma symptoms was assessed through Question #16 ("Which of Inhaler A or Inhaler B had the biggest impact on the perception of your asthma symptoms?"), which was answered only at V4 (Day 43), after revealing that the only difference between the inhalers was the color of the actuator. Subjects could choose between Inhaler A, Inhaler B, or I don't know. The number and % of subjects selecting one of the 3 options was reported separately by treatment group.

A study-specific questionnaire assessed medication use, asthma symptoms, and treatment perception through 16 questions completed via an e-Diary. Some were answered daily from V1 (Day 2) to V4 (Day 43), while others were answered at specific study visit timepoints. It included VAS, numerical, and multiple-choice questions, with VAS used for symptom perception and psychopharmacological effects. Rescue medication use was assessed through Question #2 (How many puffs of rescue medication have you taken yesterday?), answered daily every morning throughout the entire 14-day treatment period, from the day after V1 (Day 2) to the end of the study at V4 (Day 43). The average number of puffs per day was calculated for both the baseline and treatment periods, and the change from baseline was summarized separately for the ITT population by treatment group. Average value for each treatment period = mean number of puffs per day collected over Study Day 1 to Study Day 14 of each treatment period.

Asthma Quality of Life Questionnaire (AQLQ), a fully validated disease-specific tool designed to assess physical and emotional impact of asthma in adults. AQLQ consists of 32 questions divided into 4 domains: * Symptoms * Activity Limitation * Emotional Function * Environmental Stimuli Subjects were asked to respond on their condition over the previous 2 weeks via a 7-point scale, (7=not impaired at all; 1=severely impaired; higher score, better quality of life). AQLQ was administered at V2 (Day15) and V3 (Day29) via remote video calls, and V4 (Day43) via a face-to-face visit. The baseline value was defined as the last available score collected at the baseline period end (V2, Day15). The AQLQ scores were calculated as follows: Domain score = Σ scores for all items in the domain / no. of available items in that domain (0-1) AQLQ response was considered: * improved: change in score\>=0.5 * worsened: change in score\<=0.5 * no change: -0.5\<change score\<0.5

Asthma Quality of Life Questionnaire (AQLQ), a fully validated disease-specific tool designed to assess physical and emotional impact of asthma in adults. AQLQ consists of 32 questions divided into 4 domains: * Symptoms * Activity Limitation * Emotional Function * Environmental Stimuli Subjects were asked to respond on their condition over the previous 2 weeks via a 7-point scale, (7=not impaired at all; 1=severely impaired; higher score, better quality of life). AQLQ was administered at V2 (Day 15) and V3 (Day 29) via remote video calls, and V4 (Day43) via a face-to-face visit. The baseline value was defined as the last available score collected at the baseline period end (V2, Day15). The AQLQ scores were calculated as follows: Domain score = Σ scores for all items in the domain / no. of available items in that domain (0-1) AQLQ response was considered: * improved: change in score\>=0.5 * worsened: change in score\<=0.5 * no change: -0.5\<change score\<0.5

Asthma Quality of Life Questionnaire (AQLQ), a fully validated disease-specific tool designed to assess physical and emotional impact of asthma in adults. AQLQ consists of 32 questions divided into 4 domains: * Symptoms * Activity Limitation * Emotional Function * Environmental Stimuli Subjects were asked to respond on their condition over the previous 2 weeks via a 7-point scale, (7=not impaired at all; 1=severely impaired; higher score, better quality of life). AQLQ was administered at V2 (Day 15) and V3 (Day 29) via remote video calls, and V4 (Day43) via a face-to-face visit. The baseline value was defined as the last available score collected at the baseline period end (V2, Day15). The AQLQ scores were calculated as follows: Domain score = Σ scores for all items in the domain / no. of available items in that domain (0-1) AQLQ response was considered: * improved: change in score\>=0.5 * worsened: change in score\<=0.5 * no change: -0.5\<change score\<0.5

Asthma Quality of Life Questionnaire (AQLQ), a fully validated disease-specific tool designed to assess physical and emotional impact of asthma in adults. AQLQ consists of 32 questions divided into 4 domains: * Symptoms * Activity Limitation * Emotional Function * Environmental Stimuli Subjects were asked to respond on their condition over the previous 2 weeks via a 7-point scale, (7=not impaired at all; 1=severely impaired; higher score, better quality of life). AQLQ was administered at V2 (Day 15) and V3 (Day 29) via remote video calls, and V4 (Day43) via a face-to-face visit. The baseline value was defined as the last available score collected at the baseline period end (V2, Day15). The AQLQ scores were calculated as follows: Domain score = Σ scores for all items in the domain / no. of available items in that domain (0-1) AQLQ response was considered: * improved: change in score\>=0.5 * worsened: change in score\<=0.5 * no change: -0.5\<change score\<0.5

Asthma Quality of Life Questionnaire (AQLQ), a fully validated disease-specific tool designed to assess physical and emotional impact of asthma in adults. AQLQ consists of 32 questions divided into 4 domains: * Symptoms * Activity Limitation * Emotional Function * Environmental Stimuli Subjects were asked to respond on their condition over the previous 2 weeks via a 7-point scale, (7=not impaired at all; 1=severely impaired; higher score, better quality of life). AQLQ was administered at V2 (Day 15) and V3 (Day 29) via remote video calls, and V4 (Day43) via a face-to-face visit. The baseline value was defined as the last available score collected at the baseline period end (V2, Day15). Overall score = Σ scores of each 32 domains/ no. of available items in overall AQLQ (0-1)

An adverse event (AE) was defined as "any untoward medical occurrence in a patient or clinical trial subject 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". A serious adverse event (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.