Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Effect of BDP/FF/GB pMDI at therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF). |
Placebo-adjusted change in QTc interval based on the Fridericia's correction (??QTcF) after dosing CHF5993 pMDI (200/12/25 µg). Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Effect of BDP/FF/GB pMDI and GB pMDI at supra-therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF). |
Placebo-adjusted change from baseline in QTc interval based on the Fridericia's correction (??QTcF) after dosing CHF5993 pMDI (800/48/100 µg) and GB pMDI (100 µg). Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Assay sensitivity by demonstrating the effect of a single oral therapeutic dose of moxifloxacin on QTcF. |
Placebo-adjusted change from baseline in QTc interval based on the Fridericia's correction (??QTcF) after dosing 400 mg of moxifloxacin. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG |
time 0 (pre-dose) to 6 hours |
|
Secondary |
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on Hearth Rate (HR). |
Placebo-adjusted change from baseline of HR (??HR) after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg) will be summarized by means of descriptive statistics at each analysis time point and by treatment. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on PR interval (PR). |
Placebo-adjusted change from baseline of PR (??PR) after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg) will be summarized by means of descriptive statistics at each analysis time point and by treatment. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on QRS interval (QRS). |
Placebo-adjusted change from baseline of QRS (??QRS) after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg) will be summarized by means of descriptive statistics at each analysis time point and by treatment. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on individual-corrected QT interval (QTcI) |
Placebo-adjusted change from baseline in individual-corrected QT interval (??QTcI) after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Effect of moxifloxacin at therapeutic dose on individual-corrected QT interval. |
Placebo-adjusted change from baseline in individual-corrected QT interval (??QTcI) after dosing 400 mg of moxifloxacin. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 6 hours |
|
Secondary |
Changes in T-wave morphology and U-wave presence. |
Frequency of treatment-emergent changes in T-wave morphology and U-wave presence after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of categorical outliers of Hearth Rate (HR), PR interval (PR), QRS interval (QRS) and QTcF interval (QTcF), after BDP/FF/GB pMDI dosing at therapeutic and supra-therapeutic dose, and after GB dosing at supra-therapeutic dose. |
Results of categorical outliers will be summarized by treatment in frequency tables reporting: counts and percentages for number of subjects and number of time points with 1) abnormal actual QTcF values, and 2) abnormal change from baseline of HR, PR, QRS and QTcF. Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG. |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Maximum plasma concentration (Cmax), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of Cmax after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Area under the curve from 0 to 12 hours post-dose (AUC0-12), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of AUC0-12, after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Area under the plasma concentration-time curve from time 0 to time t (AUC0 t), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of AUC0-t after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Area under the curve from time 0 to infinity (AUC0-8), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of AUC0-8 after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Time to maximum plasma concentration (tmax), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of tmax, after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Analysis of Terminal half-life (t1/2), pharmacokinetic parameter of FF, GB, BDP and B17MP |
Analysis of t1/2, after dosing BDP/FF/GB pMDI (200/12/25 µg and 800/48/100 µg) and GB pMDI (100 µg). |
time 0 (pre-dose) to 24 hours |
|
Secondary |
Incidence of Adverse events |
Number and percentage of subjects with at least one event and number of treatment emergent events |
from study start through study completion, an average of 4 months |
|
Secondary |
Incidence of Adverse Drug Reactions |
Number and percentage of subjects with at least one event and number of treatment emergent events |
from study start through study completion, an average of 4 months |
|
Secondary |
Change of systolic and diastolic blood pressure |
Number and percentage of subjects with with abnormal changes from baseline |
from study start through study completion, an average of 4 months |
|
Secondary |
Body temperature abnormal values |
Number and percentage of subjects with at least one event and number of treatment emergent events |
from study start through study completion, an average of 4 months |
|
Secondary |
Abnormal results of physical examinations |
Number and percentage of subjects with at least one event and number of treatment emergent events |
from study start through study completion, an average of 4 months |
|
Secondary |
Abnormal clinical chemistry and haematology laboratory tests |
Number and percentage of subjects with at least one event and number of treatment emergent events |
from study start through study completion, an average of 4 months |
|