Efficacy and Safety of CHF 1535 200/6µg in Not Adequately Controlled Asthmatic Patients (FORCE)

A 12-week, Multinational, Multicentre, Randomised, Double-blind, Double-dummy, 2-arm Parallel Group Study Comparing the Efficacy and Safety of CHF 1535 200/6µg Versus Beclomethasone Dipropionate in Adult Asthmatic Patients Not Adequately Controlled on High Dose of Inhaled Corticosteroids or on Medium Dose of Inhaled Corticosteroids Plus Long-acting β2 Agonists

Primary objective

To show the superiority of CHF 1535 (BDP/FF) pMDI (800/24 μg per day) over BDP HFA pMDI (800 μg per day) in terms of change from baseline to the entire treatment period in average pre-dose morning peak expiratory flow (PEF) in adult asthmatic patients not adequately controlled on high doses of ICS or on medium doses of ICS plus LABA.

Secondary objective

To evaluate the effect of CHF 1535 pMDI on clinical outcome measures and other lung function parameters and to evaluate the safety and tolerability profile.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: CHF1535 200/6 µg pMDI; Drug: BDP HFA 100 µg pMDI

Detailed Description

This was a phase III, multinational, multicentre, randomised, double-blind, double-dummy, active-control, 2-arm parallel group study designed to demonstrate the superiority of CHF 1535 (200/6 μg FDC; 800/24 μg/day) vs. BDP (100 μg; 800 μg/day).

The study included the following phases:

• Pre-Screening Phase (Visit 0): conducted within a maximum of two weeks before the screening visit (Visit 1), aimed to explain the study to patients, obtain informed consent, and provide instructions on screening procedures, including medication restrictions.
• Screening Phase (Visit 1, Week -2): Patients were assessed for eligibility and transitioned to a 2-week open-label run-in period on beclomethasone dipropionate (BDP) pMDI 800 μg/day to establish a baseline .
• Randomisation Phase (Visit 2, Week 0): Patients were randomised in a 1:1 ratio to receive either CHF 1535 (800/24 µg/day) or BDP (800 µg/day) for 12 weeks, with allocation centrally assigned through an Interactive Web Response System (IWRS) to ensure balanced treatment groups.
• Investigational Phase (Treatment Period: Weeks 0-12): included six scheduled visits at Weeks 2, 4, 6, 8, 10, and 12 (end of treatment) to monitor efficacy and safety. Throughout this period, patients recorded their pre-dose morning and evening peak expiratory flow (PEF), rescue medication use, and asthma symptoms daily using an electronic peak flow meter. At each visit, key assessments were conducted to evaluate lung function (FEV1, FVC, and PEF), asthma symptom scores, and the use of both rescue and study medications. Vital signs, including heart rate and blood pressure, were monitored, while safety evaluations covered adverse events, serious adverse events, and laboratory assessments.
• Follow-Up Phase: conducted one week (+2 days) after the final visit (Visit 8) or early termination, the follow-up phase included a phone call to assess any unresolved adverse events (AEs) or new concomitant medications.

The total study duration for each participant was 16 weeks, including the 2-week run-in period, 12-week treatment phase, and 1-week follow-up. This design allowed sufficient time to evaluate the primary and secondary endpoints while ensuring a standardized baseline before randomisation.

• Study Type: Interventional
• Enrollment (Actual): 542
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Chiesi Clinical Trial Site
  • Plovdiv, Bulgaria, 4023
    • Chiesi Clinical Trial Site
  • Rousse, Bulgaria, 5402
    • Chiesi Clinical Trial Site
  • Rousse, Bulgaria, 7002
    • Chiesi Clinical Trial Site
  • Sofia, Bulgaria, 1000
    • Chiesi Clinical Trial Site
  • Sofia, Bulgaria, 1407
    • Chiesi Clinical Trial Site
  • Sofia, Bulgaria, 1510
    • Chiesi Clinical Trial Site
  • Sofia, Bulgaria, 1606
    • Chiesi Clinical Trial Site
  • Sofia, Bulgaria, 1618
    • Chiesi Clinical Trial Site
  • Stara Zagora, Bulgaria, 6000
    • Chiesi Clinical Trial Site
  • Troyan Municipality, Bulgaria, 5600
    • Chiesi Clinical Trial Site
  • Varna, Bulgaria, 1510
    • Chiesi Clinical Trial Site
  • Varna, Bulgaria, 9010
    • Chiesi Clinical Trial Site
• Czechia
  • Mělník, Czechia, 27601
    • Chiesi Clinical Trial Site
  • Neratovice, Czechia, 27711
    • Chiesi Clinical Trial Site
  • Prague, Czechia, 14000
    • Chiesi Clinical Trial Site
• France
  • Marmande, France, 47200
    • Chiesi Clinical Trial
  • Perpignan, France, 66000
    • Chiesi Clinical Trial
  • Toulon, France, 83000
    • Chiesi Clinical Trial Site
• Germany
  • Berlin, Germany, 10117
    • Chiesi Clinical Trial Site
  • Berlin, Germany, 12043
    • Chiesi Clinical Trial Site
  • Bonn, Germany, 53119
    • Chiesi Clinical Trial Site
  • Düren, Germany, 52349
    • Chiesi Clinical Trial Site
  • Hamburg, Germany, 20251
    • Chiesi Clinical Trial Site
  • Leipzig, Germany, 04207
    • Chiesi Clinical Trial Site
  • Leipzig, Germany, 04357
    • Chiesi Clinical Trial Site
  • Magdeburg, Germany, 39112
    • Chiesi Clinical Trial Site
  • Radebeul, Germany, 01445
    • Chiesi Clinical Trial Site
  • Saarbrücken, Germany, 66111
    • Chiesi Clinical Trial Site
  • Schwabach, Germany, 91126
    • Chiesi Clinical Trial Site
  • Witten, Germany, 58452
    • Chiesi Clinica Trial Site
• Hungary
  • Budapest, Hungary, H-1122
    • Chiesi Clinical Trial Site
  • Dabas, Hungary, 2370
    • Chiesi Clinical Trial Site
  • Deszk, Hungary, 6772
    • Chiesi Clinical Trial Site
  • Gödöllő, Hungary, 21100
    • Chiesi Clinical Trial Site
  • Komárom, Hungary, 2900
    • Chiesi Clinical Trial Site
  • Pécs, Hungary, 7624
    • Chiesi Clinical Trial Site
  • Siófok, Hungary, 8600
    • Chiesi Clinical Trial Site
  • Szolnok, Hungary, 5000
    • Chiesi Clinical Trial Site
  • Százhalombatta, Hungary, 2440
    • Chiesi Clinical Trial Site
• Italy
  • Padua, Italy, 35013
    • Chiesi Clinical Trial Site
  • Parma, Italy, 43125
    • Chiesi Clinical Trial Site
  • Pisa, Italy, 56124
    • Chiesi Clinical Trial Site
  • Pordenone, Italy, 323170
    • Chiesi Clinical Trial Site
  • Verona, Italy, 37134
    • Chiesi Clinical Trial Site
• Poland
  • Bialystok, Poland, 15025
    • Chiesi Clinical Trial Site
  • Bialystok, Poland, 15274
    • Chiesi Clinical Trial Site
  • Bienkówka, Poland, 34200
    • Chiesi Clinical Trial Site
  • Gdansk, Poland, 80847
    • Chiesi Clinical Trial Site
  • Giżycko, Poland, 11500
    • Chiesi Clinical Trial Site
  • Gmina Jędrzejów, Poland, 28300
    • Chiesi Clinical Trial Site
  • Katowice, Poland, 40752
    • Chiesi Clinical Trial Site
  • Katowice, Poland, 40952
    • Chiesi Clinical Trial Site
  • Lodz, Poland, 90153
    • Chiesi Clinical Trial Site
  • Lodz, Poland, 92107
    • Chiesi Clinical Trial Site
  • Lublin, Poland, 20718
    • Chiesi Clinical Trial Site
  • Ostróda, Poland, 14100
    • Chiesi Clinical Trial Site
  • Ostrów Wielkopolski, Poland, 63400
    • Chiesi Clinical Trial Site
  • Rzeszów, Poland, 35051
    • Chiesi Clinical Trial Site
• Russia
  • Moscow, Russia, 109147
    • Chiesi Clinical Trial Site
  • Moscow, Russia, 117593
    • Chiesi Clinical Trial Site
  • Saratov, Russia, 410000
    • Chiesi Clinical Trial Site
  • Yaroslavl, Russia, 150030
    • Chiesi Clinica Trial Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2SQ
    • Chiesi Clinical Trial Site
  • Chorley, United Kingdom, PR7 7NA
    • Chiesi Clinical Trial Site
  • Manchester, United Kingdom, M15 6SE
    • Chiesi Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient's written informed consent obtained prior to any study-related procedures;
2. Male or female patients aged >=18;
3. Patients with persistent asthma not optimally controlled (GINA 2010 'Management Approach Based on Control') on high doses of ICS (1000-2000 μg daily dose BDP non-extrafine or equivalent) or medium doses of ICS+LABA (500-1000 μg daily dose BDP non-extrafine or equivalent plus formoterol 24 μg or salmeterol 100 μg) at a stable dose for at least 4 weeks prior to screening; Equivalence to Medium dose High dose BDP non-extrafine 500-1000 μg > 1000-2000 μg BDP extrafine 200-400 μg > 400-800 μg Budesonide 400-800 μg > 800-1600 μg Ciclesonide 160-320 μg > 320-1280 μg Fluticasone 250-500 μg > 500-1000 μg Mometasone 400-800 μg > 800-1200 μg
4. Patients with a FEV1 > = 40% and < 80% of patient's predicted normal value and an absolute value of at least 0.9 L, after appropriate washout from bronchodilators at screening and at the end of the run-in period;
5. Patients with a positive response to the reversibility test at screening, defined as ΔFEV1 ≥ 12% and ≥ 200 mL over baseline, within 30 minutes after administration of 400 μg of salbutamol pMDI. In case this reversibility threshold was not met, the FEV1 reversibility test could be performed once before randomisation, after an appropriate wash-out from bronchodilators. Alternatively, a documented positive response to reversibility, as defined above, within the 3 months prior to the screening visit was acceptable;

6. Patients with not adequately controlled asthma evidenced by:

   a. At least one of the following at any week in the 2 previous weeks (in addition to

   FEV1 < 80% of the predicted normal value) had to be present:

   i. Daytime symptoms more than twice/week; ii. Any limitations of activities; iii. Nocturnal symptoms/awakening; iv. Need for reliever/rescue treatment more than twice/week;

   b. And a score at the Asthma Control Questionnaire© (ACQ) > 0.75. Both of the above had to be met at screening and at the end of the run-in period;

7. Presence of at least 7 available pre-dose morning PEF measurements in the run-in period;
8. Patients with a cooperative attitude and ability to be trained to correctly use the pMDI and a portable electronic peak flow meter;
9. For France only: only patients registered under a social welfare could be included in the study.

Exclusion Criteria:

Patients were not enrolled in the study if one or more of the following criteria were present:

1. Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake;
2. Seasonal (intermittent) asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitiser;
3. History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations (3 or more asthma exacerbations/year) which, in the judgement of the Investigator, could have placed the patient at undue risk;
4. Hospitalisation, emergency room (ER) admission or use of systemic corticosteroids for asthma exacerbation in the 4 weeks prior to the screening visit and during the run-in period;
5. Lower respiratory tract infection in the 4 weeks before the screening visit;
6. History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which could have interfered with data evaluation;
7. Patients who suffered from Chronic Obstructive Pulmonary Disease (COPD) as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
8. Current smokers or ex-smokers with total cumulative exposure equal or more than 5 pack-years and/or who stopped smoking one year or less prior to screening visit;
9. Any change in dose, schedule, formulation of ICS or ICS+LABAs in the 4 weeks prior to the screening visit;
10. Patients who were treated with anti-IgE antibodies;
11. Patients who were treated with long acting anti-cholinergics (tiotropium);

12. Patients who used any of the following medications prior to the screening visit and had not met the specified minimum wash-out period:

    1. Short-acting β2-agonists: 6 hours;
    2. LABA: 12 hours;
    3. Fixed combinations of an anti-cholinergic and short-acting β2-agonist: 12 hours;
    4. Short-acting anti-cholinergic: 12 hours;
    5. Systemic corticosteroids: 4 weeks;
    6. Slow release corticosteroids: 12 weeks;

13. Pregnant or lactating women or women at risk of pregnancy i.e. not using one or more of the following acceptable methods of contraception:

    1. Surgical sterilisation (e.g. bilateral tubal ligation, hysterectomy);
    2. Hormonal contraception (implantable, injectable, patch, oral);
    3. Double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) Post-menopausal women, i.e. women with at least 12 months of natural (spontaneous) amenorrhea or at least 6 months of spontaneous amenorrhea with documented serum follicle-stimulating hormone levels > 40 mIU/mL, could be enrolled. A serum pregnancy test was performed at the screening visit in women of childbearing potential;
14. Patients who had received an investigational drug within 2 months before screening visit;
15. Patients with a significant history or current evidence of heart failure, cardiomyopathy, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiovascular disease which, in the judgement of the Investigator, could have placed the patient at undue risk;
16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that could have increased the risk associated with study participation or study drug administration and, in the judgment of the Investigator, would have made the patient inappropriate for entry into this study, placed the patients at undue risk or potentially compromised the results or interpretation of the study;
17. Patients with a clinically significant abnormality at 12-lead electrocardiogram (ECG) or presenting a Fridericia-correct QT (QTcF) interval value > 450 msec in males or > 470 msec in females;
18. Patients who received a live-attenuated virus vaccination within 2 weeks prior to screening or during the run-in (inactivated influenza vaccination was acceptable provided it was not administered less than 48 hours prior to screening);
19. Patients mentally or legally incapacitated;
20. Patients with a history of alcohol or drug abuse;
21. Patients with known intolerance/hypersensitivity or contra-indication to treatment with beta-2-agonists, ICSs or propellant gases/excipients;
22. Patients with major surgery in the 3 months prior to the screening visit and/or planned surgery during the trial;
23. Patients treated with non-potassium sparing diuretics (association with potassium sparing diuretics was allowed), non-selective beta-blocking drugs, quinidine, quinidine-like anti arrhythmics, or any medication with a corrected QT (QTc) prolongation potential or a history of QTc prolongation;
24. Patients treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants, unless already taken at stable doses for at least 4 weeks before the screening visit and evidence of a normal QTc interval under these medications;
25. Patients who were receiving any therapy that could have interfered with the study drugs according to the Investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CHF 1535 200/6µg pMDI; Patients in this group received CHF 1535 pMDI, an extrafine fixed-dose combination of beclomethasone dipropionate (BDP) 200 µg and formoterol fumarate (FF) 6 µg per actuation, delivered via a pressurised metered-dose inhaler (pMDI). The total daily dose was 800 µg BDP and 24 µg FF, administered as two puffs in the morning and two in the evening, providing anti-inflammatory effects from BDP and bronchodilation from FF to address airway inflammation and airflow limitation in uncontrolled asthma. To maintain blinding and ensure a double-dummy design, participants also received a placebo inhaler, identical to the active control inhaler (BDP HFA pMDI, Qvar®) in appearance, inhalation technique, and handling, but containing an inactive propellant. The placebo was administered following the same regimen as the active control, requiring patients to inhale four puffs twice daily in addition to CHF 1535 pMDI, ensuring identical inhalation routines and eliminating bias.	Drug: CHF1535 200/6 µg pMDI; 2 inhalations BID Total Daily Dose = 800/24 µg; Other Names: Beclometasone Dipropionate/Formoterol Fumarate (BPD/FF)
Active Comparator: BDP HFA 100µg pMDI; Patients in this group received beclomethasone dipropionate (BDP) HFA pMDI, commonly known as Qvar® pMDI, a standard inhaled corticosteroid (ICS) therapy for asthma management. The prescribed daily dose was 800 µg of BDP, administered as four puffs in the morning and four in the evening. This treatment provided anti-inflammatory effects, reducing airway inflammation and improving lung function in patients with uncontrolled asthma already on high-dose ICS or medium-dose ICS plus long-acting β2-agonists (LABA). To maintain blinding and ensure the double-dummy design, participants also received a placebo inhaler identical in appearance, actuation, and handling to CHF 1535 pMDI but containing an inactive propellant with no pharmacological effect. The placebo followed the same dosing regimen as CHF 1535 pMDI, meaning that in addition to taking Qvar® pMDI four puffs twice daily, patients inhaled two puffs twice daily from the placebo inhaler to replicate the administration schedule.	Drug: BDP HFA 100 µg pMDI; 4 inhalations BID Total Daily Dose = 800 µg; Other Names: Qvar®; beclomethasone dipropionate hydrofluoralkane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to the Average of the Entire Treatment Period Reported, in the Average Pre-dose Morning Peak Expiratory Flow (PEF)	PEF is a key indicator of lung function, measuring the maximum speed of air exhaled during a forceful breath. Patients used an electronic peak flow meter (Vitalograph®) to record morning pre-dose PEF values daily, with data transmitted to an e-diary. Baseline PEF, measured during the 2-week run-in period, served as a reference for post-treatment changes. To ensure accuracy, PEF was measured before taking the study medication, following a standardized procedure. Patients inhaled deeply to total lung capacity and exhaled forcefully into the device, with the highest value from three maneuvers recorded. The device provided real-time feedback, prompting a repeat if errors occurred, such as delayed effort (>120 msec), coughing, or inconsistent results (>40 L/min variation). Higher PEF values indicate better lung function, while a decline suggests worsening obstruction.	Baseline and Throughout the 12-week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Each Inter-visit Period in Average Pre-dose Morning Peak Expiratory Flow (PEF)	PEF is a key indicator of lung function, measuring the maximum speed of air exhaled during a forceful breath. In the FORCE study, patients recorded morning pre-dose PEF values daily using an electronic peak flow meter (Vitalograph®), with data automatically transmitted to an e-diary. Baseline PEF, measured during the 2-week run-in period, served as a reference for assessing lung function changes at each inter-visit period. To ensure accuracy, PEF was measured before taking the study medication, following a standardized protocol. Patients inhaled deeply to total lung capacity and exhaled forcefully, with the highest value from three acceptable maneuvers recorded. The device provided real-time feedback, prompting retests if errors were detected, such as delayed effort (>120 msec), coughing, or inconsistent results (>40 L/min variation). Higher PEF values indicated improved lung function, while a decline suggested worsening airflow obstruction.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment)
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Pre-dose Evening PEF	PEF (Peak Expiratory Flow) was measured at home by patients using a portable electronic peak flow meter. Patients were instructed on the purpose and proper technique for PEF measurement, and detailed usage guidelines were provided. During the run-in and throughout the treatment period, PEF was monitored twice daily-once in the morning and once in the evening-prior to taking the background or study medication. PEF measurements were also recorded during study visits for informational purposes. Each measurement session consisted of three consecutive blows, with the highest value being stored in the device. The average pre-dose evening PEF was calculated as the mean of all available evening PEF measurements within a given period. If fewer than 20 valid measurements were recorded during a specific period, the average value was set as missing.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Daily PEF Variability	PEF (Peak Expiratory Flow) was measured at home using a portable electronic peak flow meter. Patients were instructed on proper measurement techniques, and detailed usage guidelines were provided. During the run-in and treatment periods, PEF was recorded twice daily (morning and evening) before taking the background or study medication. Each session consisted of three blows, with the highest value stored. Daily PEF variability was calculated as: Daily PEF variability=(Best morning PEF-Best evening PEF) / (Mean of best morning and evening PEF)×100 The average daily PEF variability for each inter-visit period and the entire treatment period was the mean of all available daily values. If fewer than 20 valid daily values were recorded, the average was set as missing.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Use of Rescue Medication	The average daily use of rescue medication was assessed at each inter-visit period and over the entire 12-week treatment period. Patients recorded the number of puffs of short-acting β2-agonists (SABA) per day using an electronic diary, ensuring accurate data collection. A decrease in rescue medication use indicated improved asthma control, while an increase suggested worsening symptoms.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Percentage of Rescue Use-free Days	The percentage of rescue use-free days indicates asthma control by measuring days when no short-acting β2-agonist (SABA) was used. In this study, the proportion of days without rescue medication use was assessed at each inter-visit period and over the entire 12-week treatment period, with baseline values from the 2-week run-in period as a reference. Patients recorded daily SABA use in an electronic diary, ensuring accurate tracking. An increase in rescue use-free days reflected improved asthma control, while a decrease suggested greater symptom burden.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Day-time Asthma Symptom Score	Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Daytime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 No symptom; Mild: aware of symptoms which can be easily tolerated; Moderate: discomfort causing interference with daily activity; Severe: inability to work/make usual activity The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score daytime = Σ〖Cough daytime score + Wheeze daytime score + Chest Tightness daytime score + Breathlessness daytime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity) where the lower the overall score daytime, the better the outcome. A lower score indicates better symptom control.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Average Total Night-time Asthma Symptom Score	Asthma symptoms (cough, wheeze, chest tightness and breathlessness) were scored, always before PEF measurements, twice daily - daytime and nighttime - as follows: Nighttime asthma symptom score (ranging 0-3, where the lower the score the better the outcome): 0 No symptom; Mild: symptoms not causing awakening; Moderate: discomfort causing awakenings; Severe: causing awakenings for most of the night / don't allow to sleep at all The average score of each symptom is the mean value of all measurements. Total average Daily Asthma Symptoms score nighttime = Σ〖Cough nighttime score + Wheeze nighttime score + Chest Tightness nighttime score + Breathlessness nighttime score〗/ Number of days with available data. The sum of the four symptoms per day ranges from 0 (no symptoms) to 12 (maximum severity), where the lower the overall score nighttime, the better the outcome. A lower score indicates better symptom control.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Percentage of Asthma Symptom-free Days	The percentage of asthma symptom-free days measures the proportion of days when patients reported no daytime or nighttime asthma symptoms, reflecting overall disease control. In this study, it was assessed at each inter-visit period and over the entire 12-week treatment period. Patients recorded symptoms daily in an electronic diary, using a 4-point scale for both daytime (shortness of breath, wheezing, chest tightness, activity limitation) and nighttime (sleep disturbances due to asthma) symptoms. A symptom-free day was defined as a day with a score of 0 for both daytime and nighttime symptoms. An increase in symptom-free days indicated better asthma control, while a decrease suggested worsening disease burden.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Each Inter-visit Period and to the Entire Treatment Period in Percentage of Asthma Control Days	The percentage of asthma symptom-free days represents the proportion of days when patients experienced no asthma symptoms, providing a measure of disease control. This outcome was evaluated at each inter-visit period and over the entire 12-week treatment period. Patients recorded daily symptoms in an electronic diary, using a 4-point scale for both daytime (0 = no symptoms, 3 = severe symptoms limiting activity) and nighttime (0 = no symptoms, 3 = symptoms severely affecting sleep) asthma symptoms. A symptom-free day was defined as a day when both daytime and nighttime symptom scores were 0. An increase in symptom-free days indicated better asthma control, while a decrease suggested worsening symptom burden.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline in Pre-dose Morning Forced Expiratory Volume in 1 Second (FEV1) at Each Timepoint	Forced Expiratory Volume in 1 second (FEV1) is a key lung function measure, quantifying the volume of air forcefully exhaled in the first second of a forced expiratory maneuver. In this study, spirometry was conducted at baseline and at scheduled visits over a 12-week period to assess the effects of CHF 1535 pMDI versus BDP HFA pMDI (Qvar®) in patients with uncontrolled asthma on high-dose ICS or medium-dose ICS+LABA. Baseline FEV1, recorded at the end of the 2-week run-in phase, served as a reference for post-treatment changes. Tests were performed under controlled conditions using calibrated spirometers, ensuring precision. Patients inhaled deeply to full capacity and exhaled forcefully into the device, completing at least three acceptable maneuvers, with the highest value recorded for analysis. FEV1 is measured in liters (L), where higher values indicate better lung function. Improvements reflect enhanced airway patency, while a decline suggests worsening obstruction.	Baseline (Visit 2, Week 0),Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline in Pre-dose Morning Forced Vital Capacity (FVC) at Each Timepoint	Forced Vital Capacity (FVC) measures the total volume of air exhaled forcefully after a deep breath, providing key insights into lung function. In this study, pre-dose morning FVC was assessed at each clinic visit and over the entire treatment period. Baseline values were recorded at the end of the 2-week run-in period and used as a reference. Spirometry was conducted before study medication intake under standardized conditions using calibrated devices. Patients inhaled deeply to full lung capacity and exhaled forcefully until no air remained, with the highest value from three acceptable maneuvers recorded. Real-time feedback ensured test accuracy, prompting retests if needed. Higher FVC values indicated improved lung function, while lower values suggested airflow limitation.	Baseline (Visit 2, Week 0), Week 2 (Visit 3),Week 4 (Visit 4), Week 6 (Visit 5),Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8, End of Treatment) and across the 12 weeks
Change From Baseline to Week 12 (Visit 8) in ACQ Score	The Asthma Control Questionnaire (ACQ) assessed asthma control using a 7-item scale, where each item was scored from 0 (no impairment) to 6 (severe impairment). The total score was the average of all items, ranging from 0 (well-controlled asthma) to 6 (poorly controlled asthma). The scale included five symptom-related questions on nighttime awakenings, activity limitation, shortness of breath, wheezing, and morning symptoms, along with one question on rescue medication use and one on lung function. Patients completed the questionnaire at clinic visits, reporting symptom frequency and impact on daily activities. A decrease in ACQ score reflected improved asthma control, with a reduction of ≥0.5 points considered clinically meaningful.	Week 12 (Visit 8)
Number of Patients With Asthma Exacerbations	Asthma exacerbations were defined as worsening respiratory symptoms requiring increased medication use or medical intervention. Moderate exacerbations included increased use of rescue medication, temporary oral corticosteroid use, or unscheduled medical visits. Severe exacerbations were episodes requiring hospitalization, emergency room visits, or prolonged corticosteroid treatment. The number of exacerbations per patient was recorded to evaluate the impact of treatment on asthma stability and disease progression.	12-week treatment period
Number of Patients With Treatment Emergent Adverse Events (TEAEs)	An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". A SAE is defined as any untoward medical occurrence or effect that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. An ADR is defined as An Adverse Drug Reaction (ADR) is defined as a harmful or unintended response to a medicinal product at normal doses used for prevention, diagnosis, or treatment. ADRs are considered causally related to the drug and can range from mild to severe, including serious outcomes such as hospitalization or life-threatening conditions.	From Week 0 to Week 14 (Follow-up)

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Pierluigi Paggiaro, MD, PhD, Cardio-Thoracic and Vascular Dept, University of Pisa

Publications and helpful links

General Publications

• Paggiaro P, Corradi M, Latorre M, Raptis H, Muraro A, Gessner C, Siergiejko Z, Scuri M, Petruzzelli S. High strength extrafine pMDI beclometasone/formoterol (200/6 mug) is effective in asthma patients not adequately controlled on medium-high dose of inhaled corticosteroids. BMC Pulm Med. 2016 Dec 9;16(1):180. doi: 10.1186/s12890-016-0335-9.

Helpful Links

• Study Record on EU Clinical Trials Register including results
• CSR Synopsis available in the CHIESI Clinical Study Register

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2012
• Primary Completion (Actual): November 29, 2012
• Study Completion (Actual): November 29, 2012

Study Registration Dates

• First Submitted: April 6, 2012
• First Submitted That Met QC Criteria: April 12, 2012
• First Posted (Estimated): April 13, 2012

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Adults; ICS/LABA therapy; Lung function improvement; CHF 1535; extrafine BDP; extrafine formoterol; fixed combo BDP - formoterol
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Organic Chemicals; Polycyclic Compounds; Amines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Alcohols; Pregnadienetriols; Amino Alcohols; Ethanolamines; Steroids, Chlorinated; Formoterol Fumarate; Beclomethasone
• Other Study ID Numbers: CCD-1005-PR-0040; 2010-020602-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No