Foster® pMDI (CHF 1535) Versus Symbicort® Turbohaler in COPD Patient (FORSYYN)

Forced Expiratory Volume in 1 second (FEV1) is a key measure of lung function that quantifies the volume of air a patient can exhale forcefully in the first second of a forced expiratory maneuver. Spirometry was conducted at baseline and at Weeks 4, 12, 18, and 24 to evaluate treatment effects in patients with moderate-to-severe COPD. Baseline FEV1, recorded during the run-in phase before randomization, served as a reference for post-treatment changes. Tests were performed under controlled conditions with calibrated equipment. Patients were seated, instructed to inhale deeply to full capacity, and exhale forcefully into the spirometer. At least three acceptable and repeatable maneuvers were completed, and the highest value was used for analysis. FEV1 is measured in liters (L), with higher values indicating better lung function. Increases in FEV1 reflect improved airway patency and reduced obstruction, while decreases indicate worsening airflow limitation.

Forced Vital Capacity (FVC) measures the total volume of air a patient can exhale forcefully after a full inhalation, offering key insights into lung function. Baseline FVC, recorded during the run-in phase before randomization, served as a reference for evaluating changes during treatment. Spirometry tests were conducted in controlled settings with calibrated, high-precision equipment to ensure accuracy and reliability. Patients performed the test while seated, inhaling deeply to full lung capacity and exhaling forcefully and completely into the spirometer. At least three acceptable maneuvers meeting predefined criteria for consistency were required, with the highest FVC value recorded for analysis. The procedure adhered to standardized protocols, including calibration of equipment before each test, coaching by trained technicians, and monitoring for quality control. FVC is measured in liters (L); higher values indicate improved lung capacity and reduced airway obstruction.

Inspiratory Capacity (IC) measures the maximum volume of air a patient can inhale after a normal exhalation, providing key insights into lung expansion and respiratory mechanics. Baseline IC, recorded during the run-in phase before randomization, was used as a reference for treatment-related changes. Spirometry tests were performed in controlled conditions using calibrated, high-precision equipment to ensure accuracy. Patients exhaled to their functional residual capacity, then inhaled deeply into the spirometer. At least three acceptable maneuvers were completed, and the highest IC value was recorded. The procedure followed standardized protocols, including pre-test calibration, technician coaching, and quality control monitoring. IC is measured in liters (L), with higher values indicating improved lung capacity, reduced restriction, and enhanced respiratory function.

Maximal Mid-Expiratory Flow (MMEF) measured the mean expiratory flow during the middle 50% of a forced vital capacity (FVC) maneuver, reflecting airflow through small airways. It was an important indicator of small airway function, often impaired in diseases like COPD. MMEF was measured using spirometry under standardized conditions with calibrated equipment. Patients inhaled deeply to full lung capacity and exhaled forcefully into the spirometer. The highest value from at least three acceptable maneuvers was recorded. MMEF was expressed in liters per second (L/sec), with lower values indicating increased resistance in small airways, a hallmark of COPD and asthma. The parameter was particularly sensitive to detecting early changes in small airway function that may not yet be apparent in larger airway measurements like FEV1 or FVC. This sensitivity made MMEF valuable for assessing treatment efficacy and progression in diseases affecting small airway mechanics.

The SGRQ is a validated tool used to assess health-related quality of life in patients with chronic respiratory diseases.

It consists of 76 items across 3 domains:

• Symptoms (0-100; the lower the score, the better the heath), evaluating frequency and severity of respiratory issues (coughing, sputum production, breathlessness etc);
• Activity (0-100; idem), measuring limitations in physical activities due to breathlessness;
• Impacts (0-100; idem), examining psychological \& social effects (feelings of stigma, loss of control, and daily life disruption etc).

Each domain score = sum of the weights of the positive items of that domain / sum of the weights of all items of that domain)*100.

Total score (0 - 100) is calculated by combining the weighted scores from each domain, with higher scores indicating a greater burden of disease and poorer quality of life. A reduction of 4 points or more in the total score is considered clinically significant.

The COPD Assessment Test (CAT) is a validated eight-item questionnaire designed to assess the impact of Chronic Obstructive Pulmonary Disease (COPD) on a patient's health status. It evaluates symptoms and quality of life, including cough, phlegm production, chest tightness, breathlessness during physical activity, sleep quality, and energy levels. Each item is scored from 0 (no impact) to 5 (severe impact), resulting in a total score range of 0 to 40, where higher scores indicate a greater disease burden and worse health status.

The CAT was completed at baseline and during scheduled clinic visits throughout the treatment period. Scores were calculated by summing the responses to all eight items. A reduction in the CAT score reflects improvement in the patient's condition, with a change of 2 points or more considered clinically significant. This outcome captures changes in the patient's quality of life and provides a direct measure of the perceived impact of COPD on daily living.

This outcome measures the frequency of moderate and severe exacerbations of Chronic Obstructive Pulmonary Disease (COPD) during the treatment period. A moderate exacerbation is defined as a worsening of respiratory symptoms requiring treatment with systemic corticosteroids, antibiotics, or both, without hospitalization. A severe exacerbation is defined as a worsening of symptoms requiring hospitalization or resulting in death. Exacerbations were recorded from the start of treatment to the final scheduled visit, using data from patient-reported symptom diaries, healthcare provider assessments, and verified medical records.

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.