Study to Compare the Effects of Z7200 And Symbicort® Turbohaler on Respiratory Imaging Parameters in Asthmatic Patients

To evaluate the particle deposition in the lungs, the Computational Fluid Dynamic (CFD) was used. With CFD, based on the computed tomography (CT) derived geometries of the airways, it is possible to measure the resistance of all airways or subdivisions such as the smaller airways starting from the 3rd bifurcation onwards. The three-dimensional (3D) reconstruction in this CT-based imaging technique allows for an accurate measurement of local volume changes in the central and peripheral airways after the administration of the product. The increased sensitivity of this technique makes it possible to detect changes in airway caliber in early stages of asthma.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

The Total Airway Resistance refers to degree of resistance to the flow of air through the respiratory tract during inspiration and expiration. The degree of resistance depends on many things, particularly the diameter of the airway and whether flow is laminar or turbulent. The higher the resistance, the worse the outcome. In healthy men and women values range between 0.22 to 0.25 kPa/l.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

The Total Airway Volume is the amount of air that can be inhaled or exhaled during one respiratory cycle. This depicts the functions of the respiratory centers, respiratory muscles and the mechanics of the lung and chest wall. The higher the volume, the better the outcome.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

6MWT = 6 Minutes Walk Test (in meters). The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The longer the walk in that timespan, the better the outcome.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

FRC = Functional Residual Capacity. It is the volume in the lungs at the end of passive expiration. It is determined by opposing forces of the expanding chest wall and the elastic recoil of the lung. A normal FRC = 1.7 to 3.5 L.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

Raw = Airway resistance. It is defined as the change in transpulmonary pressure (proximal airway pressure minus the alveolar pressure) required to produce a unit flow of gas through the airways of the lung. Are considered as normal all values up to 2.8 kPas/L

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

SRaw = Specific airway resistance: also called volumic airway resistance. sRaw is a corrected index (Raw multiplied by thoracic gas volume) that describes airway behaviour regardless of lung volume. Normal values of sRaw in adult subjects have never been formally defined. sRaw is the product of Functional Residual Capacity (FRC) and Airways Resistance (Raw) and can be calculated from the relationship of plethysmographic box pressure (Pbox) to flow during spontaneous breathing. sRaw can be derived from the tangent of the slope of box Pressure/Flow. Since Raw has a strong inverse relationship to lung volume, sRaw provides a relatively stable index with which to distinguish effects of disease from those of growth and development. sRaw is significantly increased in asthmatic patients, in those with wheezing disorders, and cystic fibrosis. It has also been shown to be a useful outcome measure for bronchodilator responsiveness studies.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

TLC = Total Lung Capacity. It is the volume of air in the lungs upon the maximum effort of inspiration. Among healthy adults, the average lung capacity is about 6 liters. Age, gender, body composition, and ethnicity are factors affecting the different ranges of lung capacity among individuals.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

Borg category (C) ratio (R) 10 scale = The original Borg CR10 Scale is used to measure the intensity of dyspnoea and fatigue during an exercise (in this case after the walk test). The original one was referred to as a numerical category scale going from 0 to 10. The top of the scale, 0 or nothing at all, means no breathlessness at all. The bottom of the scale, 10 or maximal, means the most severe breathlessness that patients have ever experienced or could imagine experiencing.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

Borg category (C) ratio (R) 10 scale = The original Borg CR10 Scale is used to measure the intensity of dyspnoea and fatigue during an exercise (in this case before the walk test). The original one was referred to as a numerical category scale going from 0 to 10. The top of the scale, 0 or nothing at all, means no breathlessness at all. The bottom of the scale, 10 or maximal, means the most severe breathlessness that patients have ever experienced or could imagine experiencing.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

The patients' inhalation profile was assessed using a respiration belt. The inhalation profile through device was to be recorded at the moment of study drug administration. Respiratory belts are useful in measuring changes in thoracic or abdominal circumference during respiration. These measurements can indicate inhalation, expiration and breathing strength and can be used to derive breathing rate and characterize breathing patterns

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

FEV1 = Forced Expiratory Volume in one second. Forced expiratory volume is the most important measurement of lung function. It measures how much air a person can exhale during a forced breath. The amount of air exhaled may be measured during the first (FEV1), second (FEV2), and/or third seconds (FEV3) of the forced breath. Values of between 80% and 120% of the average value are considered normal.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

FEV1/FVC ratio = Tiffeneau Index. It is a calculated ratio use to diagnose obstructive and restrictive lung disease. It represents the proportion of a patient's vital capacity that he/she is able to expire in the first second of forced expiration to the full forced vital capacity. The result of this ratio is expressed as FEV1%. Normal values are approximately 75%.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

FVC = Forced Vital Capacity: is the total amount of air exhaled during the FEV test. Values of between 80% and 120% of the average value are considered normal.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

MEF25 = Maximal Expiratory Flow at 25% of Forced Vital Capacity (FVC). This parameter is linked to the pathology/obstruction of small airways. Patients with airway obstruction frequently exhibit a marked decrease in MEF25.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

MEF50 = Maximal Expiratory Flow at 50% of Forced Vital Capacity (FVC). MEF50 is the flow where half of forced vital capacity (FVC) remains to be exhaled. Also this parameter is linked to the pathology/obstruction of small airways. Patients with airway obstruction frequently exhibit a marked decrease in MEF50.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

PEF = Peak Expiratory Flow: is the maximum flow rate generated during a forceful exhalation, starting from full lung inflation. PEF rate primarily reflects large airway flow and depends on the voluntary effort and muscular strength of the patient. Normal adult peak expiratory flow ranges between around 400 and 700 liters per minute, although in older it can be lower.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

VAS = Visual Analogue Scale. A VAS is typically scored by measuring the distance from the bottom of the scale (or left side if oriented horizontally) (in this case after the walk test) to the level indicated by the subject. VAS is typically represented as a vertical or horizontal line, usually 100 millimeters (mm) in length, with descriptors positioned at the extremes of the scale. These extremes go from not breathless at all/no shortness of breath at the bottom or at the far left of the line, to shortness of breath as bad as can be on the top or on the right of the line, depending on the patient's opinion.

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.

VAS = Visual Analogue Scale. A VAS is typically scored by measuring the distance from the bottom of the scale (or left side if oriented horizontally) (In this case before the walk test) to the level indicated by the subject. VAS is typically represented as a vertical or horizontal line, usually 100 millimeters (mm) in length, with descriptors positioned at the extremes of the scale. These extremes go from not breathless at all/no shortness of breath at the bottom or at the far left of the line, to shortness of breath as bad as can be on the top or on the right of the line, depending on the patient's opinion. measure of the difference in dyspnoea before and after treatment

Time frame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.

Population: Per-protocol (PP) population: all randomized patients who had correct study drug administration, without any major protocol deviations that could possibly have influenced the assessment of the product effect.