Trial Outcomes & Findings for Study to Compare the Effects of Z7200 And Symbicort® Turbohaler on Respiratory Imaging Parameters in Asthmatic Patients (NCT NCT02227394)
NCT ID: NCT02227394
Last Updated: 2022-01-27
Results Overview
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.
COMPLETED
PHASE2
20 participants
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.
2022-01-27
Participant Flow
The study procedures were explained to the patients on the screening visit day (Visit 1). Patients who wanted to participate in the study were asked to sign the ICF. Patients were given the chance to ask questions and to clarify their doubts regarding the study either at the screening visit or at any time during the study. Study procedures commenced only after the patient had signed the ICF.
Only patients who met all inclusion criteria and none of the exclusion criteria were enrolled in the study and entered the run-in period of 7 (minimum) to 31 (maximum) days.
Participant milestones
| Measure |
Z7200 - Symbicort® Turbohaler
the patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the test product (Z7200) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
Z7200: Total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01).
At visit 2 or 3 (cross-over design)
Symbicort® Turbohaler®: Total dose budesonide/formoterol is 320 mcg/9 mcg. At visit 2 or 3 (cross-over design)
|
Symbicort® Turbohaler - Z7200
the patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the first dosing day (Period 1, Visit 2), then, after a washout period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the test product (Z7200) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with a matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 320 mcg/9 mcg).
Z7200: Total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01).
At visit 2 or 3 (cross-over design)
Symbicort® Turbohaler®: Total dose budesonide/formoterol is 320 mcg/9 mcg. At visit 2 or 3 (cross-over design)
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|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Compare the Effects of Z7200 And Symbicort® Turbohaler on Respiratory Imaging Parameters in Asthmatic Patients
Baseline characteristics by cohort
| Measure |
All Patients
n=20 Participants
The results of demographic and baseline characteristics are presented for the safety population overall.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
|
Age, Continuous
|
58.5 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Total Airway Volume (iVaw)
change from predose to postdose
|
2.068 mL
Standard Deviation 1.659
|
2.255 mL
Standard Deviation 2.341
|
|
Total Airway Volume (iVaw)
predose
|
49.033 mL
Standard Deviation 13.231
|
48.577 mL
Standard Deviation 13.430
|
|
Total Airway Volume (iVaw)
postdose
|
51.101 mL
Standard Deviation 12.738
|
50.831 mL
Standard Deviation 13.478
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Total Airway Resistance (iRaw)
predose
|
0.034 kPas/L
Standard Deviation 0.016
|
0.037 kPas/L
Standard Deviation 0.022
|
|
Total Airway Resistance (iRaw)
postdose
|
0.025 kPas/L
Standard Deviation 0.011
|
0.026 kPas/L
Standard Deviation 0.009
|
|
Total Airway Resistance (iRaw)
change from predose to postdose
|
-0.008 kPas/L
Standard Deviation 0.007
|
-0.011 kPas/L
Standard Deviation 0.016
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Z7200
n=16 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=16 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Number of Deposited Particles Per Pre-defined Airway Section
Budesonide
|
776339324 Count of Particles
Standard Deviation 111075944
|
17306552 Count of Particles
Standard Deviation 6985870
|
|
Number of Deposited Particles Per Pre-defined Airway Section
Formoterol
|
80448811 Count of Particles
Standard Deviation 14821542
|
425671 Count of Particles
Standard Deviation 179309
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - FEV1
predose
|
2.935 Liters
Standard Deviation 0.904
|
2.905 Liters
Standard Deviation 0.890
|
|
Spirometry - FEV1
postdose
|
3.112 Liters
Standard Deviation 0.896
|
3.058 Liters
Standard Deviation 0.916
|
|
Spirometry - FEV1
change from predose to postdose
|
0.178 Liters
Standard Deviation 0.115
|
0.153 Liters
Standard Deviation 0.152
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - FVC
predose
|
4.317 Liters
Standard Deviation 1.113
|
4.311 Liters
Standard Deviation 1.125
|
|
Spirometry - FVC
postdose
|
4.384 Liters
Standard Deviation 1.080
|
4.328 Liters
Standard Deviation 1.155
|
|
Spirometry - FVC
change from predose to postdose
|
0.066 Liters
Standard Deviation 0.173
|
0.018 Liters
Standard Deviation 0.213
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - PEF
predose
|
7.593 L/s
Standard Deviation 1.978
|
7.465 L/s
Standard Deviation 1.869
|
|
Spirometry - PEF
postdose
|
7.912 L/s
Standard Deviation 1.948
|
7.883 L/s
Standard Deviation 1.923
|
|
Spirometry - PEF
change from predose to postdose
|
0.319 L/s
Standard Deviation 0.443
|
0.419 L/s
Standard Deviation 0.467
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - MEF25
predose
|
0.700 L/s
Standard Deviation 0.369
|
0.653 L/s
Standard Deviation 0.371
|
|
Spirometry - MEF25
postdose
|
0.873 L/s
Standard Deviation 0.490
|
0.818 L/s
Standard Deviation 0.482
|
|
Spirometry - MEF25
change from pre-dose to postdose
|
0.173 L/s
Standard Deviation 0.190
|
0.164 L/s
Standard Deviation 0.221
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - MEF50
predose
|
2.439 L/s
Standard Deviation 1.151
|
2.350 L/s
Standard Deviation 1.113
|
|
Spirometry - MEF50
postdose
|
2.878 L/s
Standard Deviation 1.265
|
2.767 L/s
Standard Deviation 1.227
|
|
Spirometry - MEF50
change from predose and postdose
|
0.440 L/s
Standard Deviation 0.353
|
0.416 L/s
Standard Deviation 0.297
|
SECONDARY outcome
Timeframe: 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%.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Spirometry - FEV1/FVC Ratio
predose
|
67.200 FEV1%
Standard Deviation 10.476
|
66.800 FEV1%
Standard Deviation 9.600
|
|
Spirometry - FEV1/FVC Ratio
postdose
|
70.600 FEV1%
Standard Deviation 10.298
|
70.600 FEV1%
Standard Deviation 9.484
|
|
Spirometry - FEV1/FVC Ratio
change from predose to postdose
|
3.400 FEV1%
Standard Deviation 2.927
|
3.800 FEV1%
Standard Deviation 2.895
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Body Plethysmography - FRC
change from predose to postdose
|
-0.176 Liters
Standard Deviation 0.228
|
-0.187 Liters
Standard Deviation 0.172
|
|
Body Plethysmography - FRC
predose
|
3.661 Liters
Standard Deviation 0.765
|
3.685 Liters
Standard Deviation 0.740
|
|
Body Plethysmography - FRC
postdose
|
3.485 Liters
Standard Deviation 0.707
|
3.498 Liters
Standard Deviation 0.717
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Body Plethysmography - TLC
predose
|
7.003 Liters
Standard Deviation 1.354
|
7.008 Liters
Standard Deviation 1.458
|
|
Body Plethysmography - TLC
postdose
|
7.007 Liters
Standard Deviation 1.376
|
6.957 Liters
Standard Deviation 1.447
|
|
Body Plethysmography - TLC
change from predose to postdose
|
0.004 Liters
Standard Deviation 0.151
|
-0.051 Liters
Standard Deviation 0.167
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Body Plethysmography - Raw
predose
|
0.398 kPas/L
Standard Deviation 0.419
|
0.411 kPas/L
Standard Deviation 0.352
|
|
Body Plethysmography - Raw
postdose
|
0.292 kPas/L
Standard Deviation 0.266
|
0.276 kPas/L
Standard Deviation 0.211
|
|
Body Plethysmography - Raw
change from predose to postdose
|
-0.106 kPas/L
Standard Deviation 0.162
|
-0.135 kPas/L
Standard Deviation 0.153
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Body Plethysmography - SRaw
predose
|
1.656 kPas
Standard Deviation 1.929
|
1.668 kPas
Standard Deviation 1.450
|
|
Body Plethysmography - SRaw
postdose
|
1.137 kPas
Standard Deviation 1.087
|
1.223 kPas
Standard Deviation 1.087
|
|
Body Plethysmography - SRaw
change from predose to postdose
|
-0.519 kPas
Standard Deviation 0.878
|
-0.445 kPas
Standard Deviation 1.066
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Z7200
n=16 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=16 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Inhalation Profile
|
2.565 Liters
Standard Deviation 0.829
|
2.366 Liters
Standard Deviation 1.618
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=19 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=19 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
6MWT
predose
|
577.789 meters
Standard Deviation 69.222
|
583.789 meters
Standard Deviation 71.707
|
|
6MWT
postdose
|
581.789 meters
Standard Deviation 72.250
|
598.158 meters
Standard Deviation 81.990
|
|
6MWT
change from predose to postdose
|
4.000 meters
Standard Deviation 12.428
|
14.368 meters
Standard Deviation 47.174
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Borg CR10 Scale (Pre-6MWT)
predose
|
0.805 score on a scale
Standard Deviation 1.160
|
0.670 score on a scale
Standard Deviation 0.933
|
|
Borg CR10 Scale (Pre-6MWT)
postdose
|
0.935 score on a scale
Standard Deviation 1.241
|
0.820 score on a scale
Standard Deviation 0.950
|
|
Borg CR10 Scale (Pre-6MWT)
change from predose to postdose
|
0.130 score on a scale
Standard Deviation 0.734
|
0.150 score on a scale
Standard Deviation 0.511
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
Borg CR10 Scale (Post-6MWT)
predose
|
1.945 score on a scale
Standard Deviation 2.029
|
1.580 score on a scale
Standard Deviation 1.265
|
|
Borg CR10 Scale (Post-6MWT)
postdose
|
1.820 score on a scale
Standard Deviation 1.753
|
1.375 score on a scale
Standard Deviation 1.290
|
|
Borg CR10 Scale (Post-6MWT)
change from pre-dose
|
-0.125 score on a scale
Standard Deviation 1.188
|
-0.205 score on a scale
Standard Deviation 0.718
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
VAS (Pre-6MWT)
|
19.550 units on a scale
Standard Deviation 29.416
|
8.150 units on a scale
Standard Deviation 25.808
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Z7200
n=20 Participants
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 Participants
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
VAS (Post-6MWT)
|
21.450 percentage of value
Standard Deviation 23.962
|
15.850 percentage of value
Standard Deviation 28.863
|
Adverse Events
Z7200
Symbicort Turbohaler
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Z7200
n=20 participants at risk
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose - consisting of two inhalations - dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
|
Symbicort Turbohaler
n=20 participants at risk
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose -- consisting of two inhalations for a total dose budesonide/formoterol is 320 mcg/9 mcg - contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations
|
|---|---|---|
|
General disorders
Influenza Like Illness
|
5.0%
1/20 • Number of events 1 • Adverse events were collected from Visit 2 (Time frame between day 7 and day 31) up to Follow-Up period (at maximum until day 83)
|
0.00%
0/20 • Adverse events were collected from Visit 2 (Time frame between day 7 and day 31) up to Follow-Up period (at maximum until day 83)
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1 • Adverse events were collected from Visit 2 (Time frame between day 7 and day 31) up to Follow-Up period (at maximum until day 83)
|
0.00%
0/20 • Adverse events were collected from Visit 2 (Time frame between day 7 and day 31) up to Follow-Up period (at maximum until day 83)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place