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

An 8-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 3 Doses of CHF 718 pMDI (HFA Beclomethasone Dipropionate Via Pressured Metered Dose Inhaler) in Asthmatic Subjects.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03084718

Acronym

BEAM

Enrollment

610

Registered

2017-03-21

Start date

2017-07-28

Completion date

2018-12-05

Last updated

2021-12-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Brief summary

The purpose of this study is to evaluate the dose-response of different doses of CHF 781 Pressurized Metered Dose Inhaler (pMDI) on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target patient population.

Detailed description

This is a phase II, multicenter, randomized, double-blind, placebo and active controlled dose ranging 5-arm parallel group study to identify the optimal dose of CHF 781 pMDI with respect to lung function and other clinical efficacy and safety outcomes. After a 2 week run-in period under rescue albuterol as needed and background inhaled corticosteroid (ICS), patients will be randomized to one of the 5 study treatment groups. After randomization, patients will be assessed after 4 and 8 weeks of study treatment at the center. A follow-up phone call will be performed a week after the last visit. During the study, daily asthma symptoms, peak expiratory flow, rescue and background medication use, and compliance with the study medication will be recorded via subject diary. Treatment-Emergent Adverse Events (TEAEs) will be assessed and recorded throughout the study. At screening and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurements, and 12-lead ECG. Routine hematology, blood chemistry, and pregnancy testing will be performed before enrollment and at end of study. 24-hr urine cortisol and creatinine will be assessed before and after the first dose and just before the last dose of study treatment.

Interventions

DRUGCHF 718 pMDI

Dose Response: Test one of three different doses of CHF 718 pMDI

DRUGPlacebo pMDI

Placebo Control

DRUGBeclomethasone Dipropionate (BDP)

Active Control

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Male or female subjects aged ≥18 and ≤75 years who have signed an Informed Consent form prior to initiation of any study-related procedure. * A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report, 2016, documented for at least 1 year prior to screening. * Subjects with poorly controlled or uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire 7 © (ACQ-7) ≥1.5 (this criterion must be met at screening and at randomization visits). * Subjects with a pre-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) ≥50% and \<85% of their predicted normal value, after appropriate washout from bronchodilators, at the screening and randomization visits. * Subjects with a positive response to a reversibility test at screening (pre - post BD), within 1 year prior to or at screening defined as ΔFEV1≥12% and ≥200 mL over baseline within 30 minutes after inhaling 4 puffs of albuterol HFA 90µg/actuation. * Use of inhaled corticosteroids (low/medium dose according to GINA Report 2016) with or without a long-acting bronchodilator (LABD) for 3 months (stable dose in the last 4 weeks) before screening visit (V). * A cooperative attitude and ability to demonstrate correct use of the diary, peak flow meter, and pMDI inhalers. * A basal morning (7-10 am) serum cortisol level between 7-28 µg/dL at screening visit (V1). * A Body Mass Index (BMI): 18.5 ≤ BMI \<35 kg/m\^2.

Exclusion criteria

* Pregnant (as evident by a positive urine human chorionic gonadotropin (hCG) or serum β-hCG test) or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use a highly effective birth control method * Subjects who suffer from chronic obstructive pulmonary disease (COPD) as defined by the GOLD Report 2017, or are suspected of having Asthma COPD Overlap Syndrome (ACOS) as defined in GINA Report, 2016. * Inability to carry out pulmonary lung function testing, to comply with study procedures or with study drug intake. * Current smokers or ex-smokers (tobacco, vapor cigarettes, marijuana) with a smoking history of \>10 pack-years or having stopped smoking one year or less prior to screening visit. * History of life-threatening asthma, clinically significant uncontrolled disease or respiratory infection. * An asthma exacerbation requiring oral corticosteroids within 3 months or hospitalization within 6 months prior to screening. * Subjects with unresolved bacterial or viral respiratory tract, sinus or middle ear infection affecting asthma status within 2 weeks prior to screening. * Subjects who received a vaccination within 2 weeks prior to screening or during the run-in. * Subjects with oral candidiasis at screening or at randomization. * Subjects with any clinically significant, uncontrolled condition * Subjects who have clinically significant cardiovascular condition * Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement. * Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) \>450 ms for males or QTcF \>470 ms for females at screening and randomization visits. * Subjects with known intolerance/hypersensitivity or contra-indication to treatment with ß2-adrenergic receptor agonists, inhaled corticosteroids or propellant gases/excipients. * Subjects with concomitant immunosuppressive therapy, use of oral or injected corticosteroids, anti-Immunoglobulin E (IgE), anti-Interleukin 5 (IL5), or other monoclonal or polyclonal antibodies within 12 weeks prior to screening. * Use of potent cytochrome P450 3A4 inhibitors and inducers within 4 weeks prior to screening. * History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening. * Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial. * Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order. * Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.

Design outcomes

Primary

Measure	Time frame	Description
Pre-dose Morning FEV1 at Week 8 - Change From Baseline	Baseline, Week 8	Change from baseline in pre-dose morning FEV1 (average of pre-dose FEV1 measurements) at Week 8. 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;

Secondary

Measure	Time frame	Description
Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Baseline, Week 4, Week 8	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;
Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Baseline, Week 4, Week 8	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;
Average Use of Rescue Medication - Change From Baseline	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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
Percentage (%) of Rescue Medication-free Days - Change From Baseline	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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
Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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
Percentage (%) of Asthma Control Days - Change From Baseline	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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
Pre-dose Morning FEV1 at Week 4 - Change From Baseline	Baseline, Week 4	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;
Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	Baseline, Week 4, Week 8	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 ECG Parameters - Heart Rate - Change From Baseline	Baseline, Week 8	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 ECG Parameters - PR, QRS, QTcF - Change From Baseline.	Baseline, Week 8	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;
12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	Baseline, Week 8	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 Urine Free Cortisol - Change From Baseline	Baseline, Week 8	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.	Baseline, Week 8	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;
Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)	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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Treatment A CHF 718 pMDI 100 µg TDD	118
Treatment B CHF 718 pMDI 400 µg TDD	116
Treatment C CHF 718 pMDI 800 µg TDD	120
Treatment D Placebo Control	124
Treatment E Beclomethasone dipropionate Hydrofluoroalkane (HFA) (QVAR\^®), Active Control Beclomethasone dipropionate Hydrofluoroalkane (HFA), Total Daily Dose (TDD) 320 µg; QVAR® 80 μg/actuation: 2 inhalations BID, Total Daily Dose (TDD) of BDP: 320 μg;	124
Total	602

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	3	5	5	8	2
Overall Study	Death	0	1	0	0	0
Overall Study	Lack of Efficacy	2	0	1	4	0
Overall Study	Lost to Follow-up	0	1	0	0	2
Overall Study	Physician Decision	1	0	0	0	0
Overall Study	Protocol Violation	0	0	1	0	0
Overall Study	Randomization error; E-diary non-compliance; Complications with device use	1	0	1	2	0
Overall Study	Withdrawal by Subject	4	3	4	0	0

Baseline characteristics

Characteristic	Total	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E
Age at first diagnosis of asthma	17.2 years STANDARD_DEVIATION 17.6	17.4 years STANDARD_DEVIATION 18.3	17.3 years STANDARD_DEVIATION 18.1	17.2 years STANDARD_DEVIATION 17.7	17.4 years STANDARD_DEVIATION 18	16.5 years STANDARD_DEVIATION 15.8
Age, Categorical <=18 years	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Age, Categorical >=65 years	80 Participants	21 Participants	15 Participants	13 Participants	12 Participants	19 Participants
Age, Categorical Between 18 and 65 years	520 Participants	97 Participants	101 Participants	107 Participants	110 Participants	105 Participants
Age, Continuous	48.1 years STANDARD_DEVIATION 14.52	50.2 years STANDARD_DEVIATION 13.58	48.1 years STANDARD_DEVIATION 14.38	48.2 years STANDARD_DEVIATION 13.83	45.4 years STANDARD_DEVIATION 16.17	48.8 years STANDARD_DEVIATION 14.24
Asthma medication category at study entry ICS/LABA/LAMA	5 Participants	2 Participants	2 Participants	0 Participants	0 Participants	1 Participants
Asthma medication category at study entry ICS/Long-Acting Muscarinic Antagonist (LAMA), (free combination)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Asthma medication category at study entry ICS/ Long-Acting β2-agonist (LABA), (free or fixed combination)	449 Participants	93 Participants	88 Participants	86 Participants	88 Participants	94 Participants
Asthma medication category at study entry Inhaled Corticosteroid (ICS) alone	147 Participants	23 Participants	26 Participants	34 Participants	36 Participants	28 Participants
Asthma medication category at study entry Leukotriene Receptor Antagonist (LTRA)	83 Participants	24 Participants	7 Participants	17 Participants	18 Participants	17 Participants
Asthma medication category at study entry SAMA/SABA	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Asthma medication category at study entry Short-Acting Muscarinic Antagonist (SAMA)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Asthma medication category at study entry Short-Acting β2-agonist (SABA), (albuterol)	592 Participants	115 Participants	115 Participants	117 Participants	124 Participants	121 Participants
Asthma medication category at study entry Theophylline	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Body Mass Index (BMI)	28.0 kg/m^2 STANDARD_DEVIATION 4.3	28.9 kg/m^2 STANDARD_DEVIATION 4	27.4 kg/m^2 STANDARD_DEVIATION 4.3	28.2 kg/m^2 STANDARD_DEVIATION 4.3	27.8 kg/m^2 STANDARD_DEVIATION 4.6	27.9 kg/m^2 STANDARD_DEVIATION 4
Duration of smoking	10.8 years STANDARD_DEVIATION 7.7	10.3 years STANDARD_DEVIATION 8.2	9.5 years STANDARD_DEVIATION 6.1	13.7 years STANDARD_DEVIATION 9.1	10.4 years STANDARD_DEVIATION 8.6	10.3 years STANDARD_DEVIATION 6.7
Ethnicity (NIH/OMB) Hispanic or Latino	166 Participants	34 Participants	34 Participants	30 Participants	40 Participants	28 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	436 Participants	84 Participants	82 Participants	90 Participants	84 Participants	96 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
FEV1 at baseline	2.155 litres STANDARD_DEVIATION 0.553	2.131 litres STANDARD_DEVIATION 0.5	2.128 litres STANDARD_DEVIATION 0.545	2.114 litres STANDARD_DEVIATION 0.531	2.268 litres STANDARD_DEVIATION 0.603	2.130 litres STANDARD_DEVIATION 0.571
FEV1/FVC at baseline	0.685 ratio of the parameters STANDARD_DEVIATION 0.102	0.696 ratio of the parameters STANDARD_DEVIATION 0.104	0.687 ratio of the parameters STANDARD_DEVIATION 0.099	0.693 ratio of the parameters STANDARD_DEVIATION 0.098	0.677 ratio of the parameters STANDARD_DEVIATION 0.104	0.675 ratio of the parameters STANDARD_DEVIATION 0.106
FEV1 (% predicted normal value) at baseline	68.5 percent of predicted normal value STANDARD_DEVIATION 8.4	68.5 percent of predicted normal value STANDARD_DEVIATION 8.4	68.3 percent of predicted normal value STANDARD_DEVIATION 7.8	68.4 percent of predicted normal value STANDARD_DEVIATION 8.7	68.6 percent of predicted normal value STANDARD_DEVIATION 8	68.8 percent of predicted normal value STANDARD_DEVIATION 8.9
FVC at baseline	3.209 litres STANDARD_DEVIATION 0.931	3.159 litres STANDARD_DEVIATION 0.971	3.164 litres STANDARD_DEVIATION 0.931	3.101 litres STANDARD_DEVIATION 0.855	3.415 litres STANDARD_DEVIATION 1.02	3.197 litres STANDARD_DEVIATION 0.851
Height	168.7 cm STANDARD_DEVIATION 9.4	169.6 cm STANDARD_DEVIATION 9.5	168.2 cm STANDARD_DEVIATION 9.2	167.8 cm STANDARD_DEVIATION 8.4	170.0 cm STANDARD_DEVIATION 9.8	167.9 cm STANDARD_DEVIATION 9.7
ICS dose before study Low daily dose	253 Participants	50 Participants	50 Participants	48 Participants	54 Participants	51 Participants
ICS dose before study Medium daily dose	349 Participants	68 Participants	66 Participants	72 Participants	70 Participants	73 Participants
Number of pack-years	3.0 pack-years	2.0 pack-years	2.7 pack-years	4.0 pack-years	3.5 pack-years	3.0 pack-years
Race (NIH/OMB) American Indian or Alaska Native	3 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	4 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Race (NIH/OMB) Black or African American	123 Participants	27 Participants	23 Participants	28 Participants	21 Participants	24 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	41 Participants	11 Participants	9 Participants	7 Participants	9 Participants	5 Participants
Race (NIH/OMB) White	430 Participants	78 Participants	82 Participants	84 Participants	93 Participants	93 Participants
Region of Enrollment United States	602 participants	118 participants	116 participants	120 participants	124 participants	124 participants
Sex: Female, Male Female	376 Participants	74 Participants	77 Participants	76 Participants	72 Participants	77 Participants
Sex: Female, Male Male	226 Participants	44 Participants	39 Participants	44 Participants	52 Participants	47 Participants
Smoking habits Ex-smoker	93 Participants	13 Participants	18 Participants	18 Participants	21 Participants	23 Participants
Smoking habits Non-smoker	509 Participants	105 Participants	98 Participants	102 Participants	103 Participants	101 Participants
Time since first diagnosis of asthma	363.8 months	372.3 months	372.8 months	373.9 months	306.6 months	385.0 months
Weight	80.0 kg STANDARD_DEVIATION 15.1	83.2 kg STANDARD_DEVIATION 14.9	77.9 kg STANDARD_DEVIATION 15.6	79.5 kg STANDARD_DEVIATION 14.5	80.5 kg STANDARD_DEVIATION 15.5	78.8 kg STANDARD_DEVIATION 14.7

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 119	1 / 120	0 / 121	0 / 124	0 / 124
other Total, other adverse events	18 / 119	8 / 120	25 / 121	28 / 124	21 / 124
serious Total, serious adverse events	1 / 119	2 / 120	2 / 121	1 / 124	0 / 124

Outcome results

Primary

Pre-dose Morning FEV1 at Week 8 - Change From Baseline

Change from baseline in pre-dose morning FEV1 (average of pre-dose FEV1 measurements) at Week 8. 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;

Time frame: Baseline, Week 8

Population: Intention to treat:~All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables) after the baseline.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Morning FEV1 at Week 8 - Change From Baseline	0.021 Litres
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Morning FEV1 at Week 8 - Change From Baseline	0.090 Litres
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Morning FEV1 at Week 8 - Change From Baseline	0.070 Litres
Treatment D (Placebo)	Pre-dose Morning FEV1 at Week 8 - Change From Baseline	-0.023 Litres
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Morning FEV1 at Week 8 - Change From Baseline	0.078 Litres

Comparison: Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.56795% CI: [-0.052, 0.14]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.01595% CI: [0.018, 0.209]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.05995% CI: [-0.003, 0.188]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.0995% CI: [-0.011, 0.15]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.23195% CI: [-0.031, 0.129]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.61295% CI: [-0.101, 0.059]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.01195% CI: [0.023, 0.18]Mixed Models Analysis

Secondary

12-lead ECG Parameters - Heart Rate - Change From Baseline

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;

Time frame: Baseline, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Value (MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - Heart Rate - Change From Baseline	0.6 bpm
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - Heart Rate - Change From Baseline	0.2 bpm
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - Heart Rate - Change From Baseline	0.4 bpm
Treatment D (Placebo)	12-lead ECG Parameters - Heart Rate - Change From Baseline	1.2 bpm
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - Heart Rate - Change From Baseline	-0.4 bpm

Secondary

12-lead ECG Parameters - Prolonged QTcF - Change From Baseline

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;

Time frame: Baseline, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 30 msec	6 Participants
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 60 msec	1 Participants
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 30 msec	4 Participants
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 60 msec	1 Participants
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 30 msec	4 Participants
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 60 msec	0 Participants
Treatment D (Placebo)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 60 msec	2 Participants
Treatment D (Placebo)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 30 msec	9 Participants
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 30 msec	3 Participants
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - Prolonged QTcF - Change From Baseline	QTcF > 60 msec	1 Participants

Secondary

12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.

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;

Time frame: Baseline, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Group	Value (MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	PR	-2.6 msec
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QTcF	1.6 msec
Treatment A (CHF 718 pMDI 100 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QRS	0.1 msec
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QRS	-1.3 msec
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	PR	1.5 msec
Treatment B (CHF 718 pMDI 400 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QTcF	0.7 msec
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QRS	0.9 msec
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	PR	-1.9 msec
Treatment C (CHF 718 pMDI 800 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QTcF	0.7 msec
Treatment D (Placebo)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	PR	-1.3 msec
Treatment D (Placebo)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QTcF	4.6 msec
Treatment D (Placebo)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QRS	-0.5 msec
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QRS	-0.3 msec
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	PR	1.0 msec
Treatment E (QVAR^®, 320 µg TDD)	12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.	QTcF	1.2 msec

Secondary

24-hr Creatinine - Change From Baseline.

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;

Time frame: Baseline, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Value (MEDIAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	24-hr Creatinine - Change From Baseline.	0.00 umol/mol
Treatment B (CHF 718 pMDI 400 µg TDD)	24-hr Creatinine - Change From Baseline.	0.00 umol/mol
Treatment C (CHF 718 pMDI 800 µg TDD)	24-hr Creatinine - Change From Baseline.	0.00 umol/mol
Treatment D (Placebo)	24-hr Creatinine - Change From Baseline.	0.00 umol/mol
Treatment E (QVAR^®, 320 µg TDD)	24-hr Creatinine - Change From Baseline.	0.00 umol/mol

Secondary

24-hr Urine Free Cortisol - Change From Baseline

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;

Time frame: Baseline, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Value (MEDIAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	24-hr Urine Free Cortisol - Change From Baseline	-3.60 nmol/day
Treatment B (CHF 718 pMDI 400 µg TDD)	24-hr Urine Free Cortisol - Change From Baseline	-5.35 nmol/day
Treatment C (CHF 718 pMDI 800 µg TDD)	24-hr Urine Free Cortisol - Change From Baseline	-4.10 nmol/day
Treatment D (Placebo)	24-hr Urine Free Cortisol - Change From Baseline	1.40 nmol/day
Treatment E (QVAR^®, 320 µg TDD)	24-hr Urine Free Cortisol - Change From Baseline	-3.50 nmol/day

Secondary

Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline

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;

Time frame: Baseline, Week 4, Week 8

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 4	-0.43 score on a scale
Treatment A (CHF 718 pMDI 100 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 8	-0.53 score on a scale
Treatment B (CHF 718 pMDI 400 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 4	-0.53 score on a scale
Treatment B (CHF 718 pMDI 400 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 8	-0.58 score on a scale
Treatment C (CHF 718 pMDI 800 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 4	-0.49 score on a scale
Treatment C (CHF 718 pMDI 800 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 8	-0.66 score on a scale
Treatment D (Placebo)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 8	-0.43 score on a scale
Treatment D (Placebo)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 4	-0.27 score on a scale
Treatment E (QVAR^®, 320 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 4	-0.47 score on a scale
Treatment E (QVAR^®, 320 µg TDD)	Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline	Week 8	-0.64 score on a scale

Comparison: Week 4~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.05395% CI: [-0.31, 0]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00195% CI: [-0.42, -0.11]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.00695% CI: [-0.37, -0.06]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.17695% CI: [-0.26, 0.05]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.42395% CI: [-0.22, 0.09]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.57495% CI: [-0.11, 0.2]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.01195% CI: [-0.35, -0.05]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebop-value: 0.21595% CI: [-0.27, 0.06]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.0795% CI: [-0.32, 0.01]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.00595% CI: [-0.4, -0.07]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.56695% CI: [-0.21, 0.12]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.12495% CI: [-0.29, 0.04]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.33695% CI: [-0.25, 0.08]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.0195% CI: [-0.37, -0.05]Mixed Models Analysis

Secondary

Average Use of Rescue Medication - Change From Baseline

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

Time frame: Baseline (average of the 2-week run-in period); Inter-visit period 1 (average of the first 4 weeks); Inter-visit period 2 (average of the last 4 weeks); Entire treatment period (average of 8 weeks)

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 1	-0.11 puffs/day
Treatment A (CHF 718 pMDI 100 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Entire treatment period	-0.11 puffs/day
Treatment A (CHF 718 pMDI 100 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 2	-0.12 puffs/day
Treatment B (CHF 718 pMDI 400 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 2	-0.35 puffs/day
Treatment B (CHF 718 pMDI 400 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 1	-0.27 puffs/day
Treatment B (CHF 718 pMDI 400 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Entire treatment period	-0.31 puffs/day
Treatment C (CHF 718 pMDI 800 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 2	-0.25 puffs/day
Treatment C (CHF 718 pMDI 800 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 1	-0.14 puffs/day
Treatment C (CHF 718 pMDI 800 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Entire treatment period	-0.20 puffs/day
Treatment D (Placebo)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 1	0.07 puffs/day
Treatment D (Placebo)	Average Use of Rescue Medication - Change From Baseline	Entire treatment period	0.04 puffs/day
Treatment D (Placebo)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 2	0.01 puffs/day
Treatment E (QVAR^®, 320 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 2	-0.18 puffs/day
Treatment E (QVAR^®, 320 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Inter-visit period 1	-0.13 puffs/day
Treatment E (QVAR^®, 320 µg TDD)	Average Use of Rescue Medication - Change From Baseline	Entire treatment period	-0.15 puffs/day

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.06795% CI: [-0.38, 0.01]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.53, -0.14]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.03895% CI: [-0.4, -0.01]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.1395% CI: [-0.35, 0.05]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.81195% CI: [-0.22, 0.17]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.20295% CI: [-0.07, 0.33]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.04495% CI: [-0.39, -0.01]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.28395% CI: [-0.37, 0.11]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00395% CI: [-0.6, -0.13]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.02795% CI: [-0.5, -0.03]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.05495% CI: [-0.48, 0]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.25895% CI: [-0.38, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.42395% CI: [-0.14, 0.34]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.11195% CI: [-0.42, 0.04]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.13595% CI: [-0.36, 0.05]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.56, -0.14]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.02495% CI: [-0.44, -0.03]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.06795% CI: [-0.4, 0.01]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.44495% CI: [-0.29, 0.13]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.28595% CI: [-0.09, 0.32]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.0695% CI: [-0.4, 0.01]Mixed Models Analysis

Secondary

Overall Daily Asthma Symptoms Scores - Change From Baseline

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 1	-0.1 score on a scale
Treatment A (CHF 718 pMDI 100 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Entire treatment period	-0.1 score on a scale
Treatment A (CHF 718 pMDI 100 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 2	-0.1 score on a scale
Treatment B (CHF 718 pMDI 400 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 2	-0.1 score on a scale
Treatment B (CHF 718 pMDI 400 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 1	-0.1 score on a scale
Treatment B (CHF 718 pMDI 400 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Entire treatment period	-0.1 score on a scale
Treatment C (CHF 718 pMDI 800 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 2	-0.1 score on a scale
Treatment C (CHF 718 pMDI 800 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 1	-0.1 score on a scale
Treatment C (CHF 718 pMDI 800 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Entire treatment period	-0.1 score on a scale
Treatment D (Placebo)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 1	0.0 score on a scale
Treatment D (Placebo)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Entire treatment period	0.0 score on a scale
Treatment D (Placebo)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 2	-0.0 score on a scale
Treatment E (QVAR^®, 320 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 2	-0.1 score on a scale
Treatment E (QVAR^®, 320 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Inter-visit period 1	-0.1 score on a scale
Treatment E (QVAR^®, 320 µg TDD)	Overall Daily Asthma Symptoms Scores - Change From Baseline	Entire treatment period	-0.1 score on a scale

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.91395% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.87195% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.95895% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.0195% CI: [-0.2, 0]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.01195% CI: [-0.2, 0]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.00295% CI: [-0.2, 0]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.99695% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.63295% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.6395% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.00295% CI: [-0.2, 0]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00195% CI: [-0.2, 0]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.9695% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.72595% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.76495% CI: [-0.1, 0.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: <0.00195% CI: [-0.2, -0.1]Mixed Models Analysis

Secondary

Percentage (%) of Asthma Control Days - Change From Baseline

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 1	7.3 % of asthma control days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Entire treatment period	10.8 % of asthma control days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 2	14.3 % of asthma control days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 2	16.3 % of asthma control days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 1	10.6 % of asthma control days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Entire treatment period	13.4 % of asthma control days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 2	17.5 % of asthma control days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 1	10.4 % of asthma control days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Entire treatment period	13.9 % of asthma control days
Treatment D (Placebo)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 1	5.0 % of asthma control days
Treatment D (Placebo)	Percentage (%) of Asthma Control Days - Change From Baseline	Entire treatment period	7.7 % of asthma control days
Treatment D (Placebo)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 2	10.5 % of asthma control days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 2	20.63 % of asthma control days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Inter-visit period 1	12.8 % of asthma control days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Control Days - Change From Baseline	Entire treatment period	16.7 % of asthma control days

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.42695% CI: [-3.4, 7.9]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.05595% CI: [-0.1, 11.2]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.05995% CI: [-0.2, 11.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.26395% CI: [-2.5, 9]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.2895% CI: [-2.6, 8.8]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.96595% CI: [-5.9, 5.6]Mixed Models Analysis

Comparison: Inter-visit period 1~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.00795% CI: [2.2, 13.3]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.30895% CI: [-3.5, 11.2]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.12495% CI: [-1.6, 13.2]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.06395% CI: [-0.4, 14.3]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.60295% CI: [-5.5, 9.4]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.40295% CI: [-4.3, 10.6]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.75395% CI: [-6.3, 8.6]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.00695% CI: [2.9, 17.4]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.33195% CI: [-3.1, 9.2]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.07395% CI: [-0.5, 11.9]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.04895% CI: [0.1, 12.4]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.4195% CI: [-3.6, 8.9]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.3295% CI: [-3.1, 9.4]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.86795% CI: [-5.7, 6.8]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.00495% CI: [2.9, 15]Mixed Models Analysis

Secondary

Percentage (%) of Asthma Symptoms-free Days - Change From Baseline

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 1	8.6 % of of asthma symptom-free days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Entire treatment period	12.5 % of of asthma symptom-free days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 2	16.4 % of of asthma symptom-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 2	17.0 % of of asthma symptom-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 1	10.5 % of of asthma symptom-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Entire treatment period	13.8 % of of asthma symptom-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 2	17.2 % of of asthma symptom-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 1	10.1 % of of asthma symptom-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Entire treatment period	13.6 % of of asthma symptom-free days
Treatment D (Placebo)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 1	5.7 % of of asthma symptom-free days
Treatment D (Placebo)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Entire treatment period	8.7 % of of asthma symptom-free days
Treatment D (Placebo)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 2	11.7 % of of asthma symptom-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 2	21.2 % of of asthma symptom-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Inter-visit period 1	12.8 % of of asthma symptom-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Asthma Symptoms-free Days - Change From Baseline	Entire treatment period	17.0 % of of asthma symptom-free days

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.31695% CI: [-2.8, 8.7]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.09795% CI: [-0.9, 10.7]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.12895% CI: [-1.3, 10.2]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.51195% CI: [-3.9, 7.8]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.6195% CI: [-4.3, 7.3]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.88295% CI: [-6.3, 5.4]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.01395% CI: [1.5, 12.9]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.21995% CI: [-2.8, 12.2]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.16695% CI: [-2.2, 12.8]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.15195% CI: [-2, 12.9]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.87195% CI: [-6.9, 8.2]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.83795% CI: [-6.8, 8.3]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.96695% CI: [-7.4, 7.7]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.01295% CI: [2.1, 16.9]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.23395% CI: [-2.5, 10.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.11395% CI: [-1.2, 11.4]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.1295% CI: [-1.3, 11.2]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.69195% CI: [-5.1, 7.6]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.72295% CI: [-5.2, 7.5]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.96695% CI: [-6.5, 6.2]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.00895% CI: [2.2, 14.5]Mixed Models Analysis

Secondary

Percentage (%) of Rescue Medication-free Days - Change From Baseline

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 1	5.9 % of rescue medication-free days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Entire treatment period	7.4 % of rescue medication-free days
Treatment A (CHF 718 pMDI 100 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 2	8.9 % of rescue medication-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 2	13.1 % of rescue medication-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 1	9.0 % of rescue medication-free days
Treatment B (CHF 718 pMDI 400 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Entire treatment period	11.1 % of rescue medication-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 2	10.0 % of rescue medication-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 1	6.1 % of rescue medication-free days
Treatment C (CHF 718 pMDI 800 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Entire treatment period	8.1 % of rescue medication-free days
Treatment D (Placebo)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 1	1.5 % of rescue medication-free days
Treatment D (Placebo)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Entire treatment period	2.8 % of rescue medication-free days
Treatment D (Placebo)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 2	4.1 % of rescue medication-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 2	11.2 % of rescue medication-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Inter-visit period 1	7.7 % of rescue medication-free days
Treatment E (QVAR^®, 320 µg TDD)	Percentage (%) of Rescue Medication-free Days - Change From Baseline	Entire treatment period	9.5 % of rescue medication-free days

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.11595% CI: [-1.1, 10]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00895% CI: [2, 13.1]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.09995% CI: [-0.9, 10.2]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.27595% CI: [-2.5, 8.8]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.94395% CI: [-5.4, 5.8]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.30895% CI: [-8.6, 2.7]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.02495% CI: [0.8, 11.7]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.12995% CI: [-1.4, 11]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00495% CI: [2.8, 15.2]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.06195% CI: [-0.3, 12.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.1895% CI: [-2, 10.5]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.72195% CI: [-5.1, 7.4]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.32895% CI: [-9.4, 3.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.02295% CI: [1, 13.2]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.10195% CI: [-0.9, 10.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00395% CI: [2.8, 13.9]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.06195% CI: [-0.2, 10.8]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.19695% CI: [-1.9, 9.3]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.81495% CI: [-4.9, 6.3]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.29195% CI: [-8.6, 2.6]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.01695% CI: [1.3, 12.1]Mixed Models Analysis

Secondary

Pre-dose Morning FEV1 at Week 4 - Change From Baseline

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;

Time frame: Baseline, Week 4

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Morning FEV1 at Week 4 - Change From Baseline	0.021 Litres
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Morning FEV1 at Week 4 - Change From Baseline	0.120 Litres
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Morning FEV1 at Week 4 - Change From Baseline	0.073 Litres
Treatment D (Placebo)	Pre-dose Morning FEV1 at Week 4 - Change From Baseline	0.003 Litres
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Morning FEV1 at Week 4 - Change From Baseline	0.077 Litres

Comparison: Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.64795% CI: [-0.06, 0.097]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.00495% CI: [0.039, 0.196]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.07695% CI: [-0.008, 0.149]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.01495% CI: [0.02, 0.179]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.19295% CI: [-0.026, 0.131]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.24495% CI: [-0.126, 0.032]Mixed Models Analysis

Comparison: Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.0695% CI: [-0.003, 0.151]Mixed Models Analysis

Secondary

Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline

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;

Time frame: Baseline, Week 4, Week 8

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 4	0.036 Litres
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 8	0.014 Litres
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 4	0.099 Litres
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 8	0.089 Litres
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 4	0.066 Litres
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 8	0.036 Litres
Treatment D (Placebo)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 8	-0.016 Litres
Treatment D (Placebo)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 4	0.023 Litres
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 4	0.056 Litres
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline	Week 8	0.063 Litres

Comparison: Week 4~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.7895% CI: [-0.074, 0.098]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.08695% CI: [-0.011, 0.162]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.32495% CI: [-0.043, 0.129]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.15395% CI: [-0.024, 0.15]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.48295% CI: [-0.055, 0.117]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.46395% CI: [-0.119, 0.054]Mixed Models Analysis

Comparison: Week 4~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.45395% CI: [-0.052, 0.117]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.53395% CI: [-0.064, 0.123]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.02995% CI: [0.011, 0.199]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.27495% CI: [-0.041, 0.146]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.11995% CI: [-0.019, 0.169]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.63895% CI: [-0.071, 0.116]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.27495% CI: [-0.147, 0.042]Mixed Models Analysis

Comparison: Week 8~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.09295% CI: [-0.013, 0.171]Mixed Models Analysis

Secondary

Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 1	-2 Liters/min
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Entire treatment period	-3 Liters/min
Treatment A (CHF 718 pMDI 100 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 2	-4 Liters/min
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 2	3 Liters/min
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 1	-3 Liters/min
Treatment B (CHF 718 pMDI 400 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Entire treatment period	0.3 Liters/min
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 2	-5 Liters/min
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 1	-4 Liters/min
Treatment C (CHF 718 pMDI 800 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Entire treatment period	-4 Liters/min
Treatment D (Placebo)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 1	-6 Liters/min
Treatment D (Placebo)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Entire treatment period	-4.9 Liters/min
Treatment D (Placebo)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 2	-4 Liters/min
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 2	2 Liters/min
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Inter-visit period 1	0 Liters/min
Treatment E (QVAR^®, 320 µg TDD)	Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline	Entire treatment period	1 Liters/min

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.2695% CI: [-3.2, 11.9]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.38795% CI: [-4.2, 10.9]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.57495% CI: [-5.4, 9.7]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.79995% CI: [-8.6, 6.7]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.57795% CI: [-9.8, 5.5]Mixed Models Analysis

Comparison: Inter-visit period 1~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.76495% CI: [-8.8, 6.5]Mixed Models Analysis

Comparison: Inter-visit period 1~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.09795% CI: [-1.1, 13.8]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.90895% CI: [-9.9, 8.8]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.13595% CI: [-2.2, 16.5]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebop-value: 0.78695% CI: [-10.7, 8.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.10995% CI: [-1.7, 17.1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.87695% CI: [-10.1, 8.7]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.0895% CI: [-17.9, 1]Mixed Models Analysis

Comparison: Inter-visit period 2~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.20295% CI: [-3.2, 15.3]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment A (CHF 718 pMDI 100 µg TDD) vs Treatment D (Placebo)p-value: 0.63595% CI: [-5.9, 9.7]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment D (Placebo)p-value: 0.19195% CI: [-2.6, 13.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment D (Placebo)p-value: 0.91495% CI: [-7.4, 8.3]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment B (CHF 718 pMDI 400 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.40795% CI: [-4.6, 11.3]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment A (CHF 718 pMDI 100 µg TDD)p-value: 0.71895% CI: [-9.4, 6.4]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment C (CHF 718 pMDI 800 µg TDD) vs Treatment B (CHF 718 pMDI 400 µg TDD)p-value: 0.23595% CI: [-12.7, 3.1]Mixed Models Analysis

Comparison: Entire treatment period~Comparison treatment groups were:~Treatment E (QVAR\^®, 320 µg TDD) vs Treatment D (Placebo)p-value: 0.11895% CI: [-1.6, 13.9]Mixed Models Analysis

Secondary

Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline

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;

Time frame: Baseline, Week 4, Week 8

Population: Safety population:~All randomized patients who received at least one dose of study treatment.

Arm	Measure	Group	Value (MEAN)
Treatment A (CHF 718 pMDI 100 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 4	-0.4 mmHg
Treatment A (CHF 718 pMDI 100 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 8	1.0 mmHg
Treatment A (CHF 718 pMDI 100 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 4	-0.1 mmHg
Treatment A (CHF 718 pMDI 100 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 8	0.8 mmHg
Treatment B (CHF 718 pMDI 400 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 4	1.0 mmHg
Treatment B (CHF 718 pMDI 400 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 8	1.0 mmHg
Treatment B (CHF 718 pMDI 400 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 8	2.5 mmHg
Treatment B (CHF 718 pMDI 400 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 4	0.2 mmHg
Treatment C (CHF 718 pMDI 800 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 8	0.3 mmHg
Treatment C (CHF 718 pMDI 800 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 8	0.8 mmHg
Treatment C (CHF 718 pMDI 800 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 4	-0.8 mmHg
Treatment C (CHF 718 pMDI 800 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 4	0.5 mmHg
Treatment D (Placebo)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 4	0.6 mmHg
Treatment D (Placebo)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 8	0.2 mmHg
Treatment D (Placebo)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 8	-0.5 mmHg
Treatment D (Placebo)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 4	0.1 mmHg
Treatment E (QVAR^®, 320 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 8	1.2 mmHg
Treatment E (QVAR^®, 320 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	DBP, Week 4	0.8 mmHg
Treatment E (QVAR^®, 320 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 8	-0.9 mmHg
Treatment E (QVAR^®, 320 µg TDD)	Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline	SBP, Week 4	0.0 mmHg

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026

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

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Pre-dose Morning FEV1 at Week 8 - Change From Baseline

12-lead ECG Parameters - Heart Rate - Change From Baseline

12-lead ECG Parameters - Prolonged QTcF - Change From Baseline

12-lead ECG Parameters - PR, QRS, QTcF - Change From Baseline.

24-hr Creatinine - Change From Baseline.

24-hr Urine Free Cortisol - Change From Baseline

Asthma Control Questionnaire-7© (ACQ-7) Score at Week 4 and Week 8 - Change From Baseline

Average Use of Rescue Medication - Change From Baseline

Overall Daily Asthma Symptoms Scores - Change From Baseline

Percentage (%) of Asthma Control Days - Change From Baseline

Percentage (%) of Asthma Symptoms-free Days - Change From Baseline

Percentage (%) of Rescue Medication-free Days - Change From Baseline

Pre-dose Morning FEV1 at Week 4 - Change From Baseline

Pre-dose Morning FVC at Week 4 and 8 - Change From Baseline

Pre-dose Peak Expiratory Flow (PEF) (L/Min) (Morning and Evening) - Change From Baseline

Vital Signs (Systolic and Diastolic Blood Pressure) - Change From Baseline