An 8-week Dose Ranging Study of CHF 718 pMDI in Asthmatic Subjects

Change from baseline in pre-dose morning FEV1 at Week 4.

Spirometry, used to measure FEV1, was performed according to internationally accepted standards.

Definitions:

Baseline=Baseline values for pre-dose FEV1 were the average of measurements taken at V2 (Week 0) at 45 minutes and 15 minutes pre-dose; FEV1=Forced expiratory volume in the 1st second;

Change from baseline in pre-dose morning FVC at Week 4 and 8.

Spirometry, used to measure FVC, was performed according to internationally accepted standards.

Definitions:

Baseline=Baseline values for pre-dose FVC were the average of measurements taken at V2 (Week 0) at 45 minutes and 15 minutes pre-dose; FVC=Forced vital capacity;

The ACQ consists of 7 items: 6 simple self-administered questions referring to asthma control and rescue treatment usage with 1 week recall, and a 7th item consisting of the percent (%) predicted FEV1 completed by clinic staff. Scoring uses a 7-point scale: 0 = "totally controlled" and 6 = "severely uncontrolled". The ACQ score was calculated as the average of all 7 items.

Definitions:

ACQ-7 score=Asthma Control Questionnaire-7©; Information regarding the American Thoracic Society ACQ questionnaire is also available at: https://member.thoracic.org/members/assemblies/assemblies/srn/questionaires/acq.php; Baseline ACQ-7 score = ACQ score recorded at V2 (Week 0) Day 1, before randomization; FEV1=Forced expiratory volume in the 1st second;

Change from baseline in average use of rescue medication, during Inter-visit period 1, Inter-visit period 2, Entire treatment period.

Definitions:

Baseline=For the efficacy variable -- average use of rescue medication -- derived from the electronic diary (eDiary), baseline values were the averages recorded during the run-in period;

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Change from baseline in percentage (%) of rescue medication-free days. An increased value indicates improvement from baseline.

Definitions:

Baseline=For the efficacy variable -- percentage (%) of rescue medication-free days -- derived from the electronic diary (eDiary), baseline values were the averages/percentages recorded during the run-in period.

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Overall daily asthma symptoms scores - Change From Baseline (am and pm).

Subjects had to record asthma symptom score (overall symptoms, cough, wheeze, chest tightness and breathlessness) in the am (night-time asthma symptom score) and in the pm (daytime asthma symptom score). These data were collected in the subject's diary. Daily asthma symptoms score were performed separately for am score and pm score and also as a total, where the total equals the sum of the am and pm scores. Degree of asthma symptoms by score: 0=None, 1=Mild, 2=Moderate, and 3=Severe.

Baseline=Averages values during the run-in period;

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Change from baseline in Percentage (%) of asthma symptoms-free days.

Asthma symptoms-free days is the number of days with a total asthma score=0 (daily morning plus evening asthma score).

Subjects recorded asthma symptom score as described in the Outcome measure #7.

Definitions:

Baseline=For the efficacy variables -- daytime and night-time asthma symptom scores -- derived from the eDiary, baseline values were the averages/percentages recorded during the run-in period;

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Change from baseline in percentage (%) of asthma control days, during Inter-visit period 1, Inter-visit period 2, Entire treatment period.

This outcome measure was calculated according to the following definition: Days with a total daily morning + evening asthma score = 0 AND No rescue medication use.

Definitions:

Baseline=For the efficacy variable -- asthma control days -- derived from the eDiary, baseline values were the averages/percentages recorded during the run-in period;

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Change from baseline in pre-dose Peak Expiratory Flow (PEF) (Liters/min), morning and evening measurements.

Definitions:

Baseline=For the efficacy variable -- morning and evening PEF -- derived from the eDiary, the baseline values were the averages/percentages recorded during the run-in period; PEF=evening peak expiratory flow;

Inter-visit period 1=Starts from the pm assessment of the Start of the Randomized Treatment Period to the am assessment at Visit 3 (Week 4);

Inter-visit Period 2=Starts from the pm assessment of the day the subject returns to the clinic (Visit 3) to the am assessment of the date of Visit 4 (Week 8);

Entire treatment period=Average of 8 weeks;

am=morning pm=evening

Vital signs (systolic and diastolic blood pressure) at baseline, week 4, and week 8.

Change from baseline.

Definitions:

Baseline=Baseline values were defined at visit 2 (Week 0) pre-dose; DBP=Diastolic blood pressure; SBP=Systolic blood pressure;

12-lead electrocardiogram (12-lead ECG) parameter - heart rate (HR) was measured at baseline (Day 1) and Week 8.

Change from baseline.

Definitions:

Baseline=Baseline values were defined at visit 2 (Week 0) pre-dose;

bpm=Beats per minute;

12-lead electrocardiogram (12-lead ECG) parameters - PR, QRS, QTcF intervals - were measured at baseline (Day 1) and Week 8.

Changes from baseline.

Definitions:

Baseline=Baseline values were defined at visit 2 (Week 0); QTcF=Fridericia-corrected QT interval; msec=Millisecond;

Number of participants with prolonged QTcF. Change from baseline.

Baseline=Baseline values were defined at visit 2 (Week 0) pre-dose; QTcF=Fridericia-corrected QT interval;

24-hr Urinary Free Cortisol - Change From Baseline.

For the evaluation of the 24-hr Urine-Free cortisol excretion, 24-hour urine samples were collected. Urine-free cortisol was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Definitions:

Baseline=Baseline values were defined at visit 2 (Week 0) pre-dose;

24-hr Creatinine - Change From Baseline.

For the evaluation of the 24-hr creatinine excretion, 24-hour urine sample were collected. Creatinine was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Definitions:

Baseline=Baseline values were defined at visit 2 (Week 0) pre-dose;