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

NCT01577082 | Completed Phase 3 Results

• 2 other identifiers: CCD-1005-PR-00402010-020602-14
• Study Type: interventional
• Target: 542
• Locations: 9 countries
• Sites: 66

Brief Summary

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.

Conditions

Asthma

Keywords

Adults; ICS/LABA therapy; Lung function improvement; CHF 1535; extrafine BDP; extrafine formoterol; fixed combo BDP - formoterol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change From Baseline to Each Inter-visit Period in Average Pre-dose Morning Peak Expiratory Flow (PEF)

  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

  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

  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

  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

  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

Study Arms (2)

CHF 1535 200/6µg pMDI

EXPERIMENTAL

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

BDP HFA 100µg pMDI

ACTIVE COMPARATOR

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

Interventions

CHF1535 200/6 µg pMDI DRUG

2 inhalations BID Total Daily Dose = 800/24 µg

Also known as: Beclometasone Dipropionate/Formoterol Fumarate (BPD/FF)

CHF 1535 200/6µg pMDI

BDP HFA 100 µg pMDI DRUG

4 inhalations BID Total Daily Dose = 800 µg

Also known as: Qvar®, beclomethasone dipropionate hydrofluoralkane

BDP HFA 100µg pMDI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's written informed consent obtained prior to any study-related procedures;
• Male or female patients aged \>=18;
• 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
• 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;
• 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;
• 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;
• Presence of at least 7 available pre-dose morning PEF measurements in the run-in period;
• Patients with a cooperative attitude and ability to be trained to correctly use the pMDI and a portable electronic peak flow meter;
• For France only: only patients registered under a social welfare could be included in the study.

You may not qualify if:

• Patients were not enrolled in the study if one or more of the following criteria were present:
• Inability to carry out pulmonary lung function testing, to comply with study procedures or with study treatment intake;
• Seasonal (intermittent) asthma or asthma occurring only during episodic exposure to an allergen or a chemical sensitiser;
• 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;
• 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;
• Lower respiratory tract infection in the 4 weeks before the screening visit;
• History of cystic fibrosis, bronchiectasis or alpha-1 antitrypsin deficiency, or any other significant lung disease which could have interfered with data evaluation;
• Patients who suffered from Chronic Obstructive Pulmonary Disease (COPD) as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
• 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;
• Any change in dose, schedule, formulation of ICS or ICS+LABAs in the 4 weeks prior to the screening visit;
• Patients who were treated with anti-IgE antibodies;
• Patients who were treated with long acting anti-cholinergics (tiotropium);
• Patients who used any of the following medications prior to the screening visit and had not met the specified minimum wash-out period:
• Short-acting β2-agonists: 6 hours;
• LABA: 12 hours;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (66)

Chiesi Clinical Trial Site

Plovdiv, 4004, Bulgaria

Location

Chiesi Clinical Trial Site

Plovdiv, 4023, Bulgaria

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Chiesi Clinical Trial Site

Rousse, 5402, Bulgaria

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Chiesi Clinical Trial Site

Rousse, 7002, Bulgaria

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Chiesi Clinical Trial Site

Sofia, 1000, Bulgaria

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Chiesi Clinical Trial Site

Sofia, 1407, Bulgaria

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Chiesi Clinical Trial Site

Sofia, 1510, Bulgaria

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Chiesi Clinical Trial Site

Sofia, 1606, Bulgaria

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Chiesi Clinical Trial SIte

Sofia, 1618, Bulgaria

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Chiesi Clinical Trial Site

Stara Zagora, 6000, Bulgaria

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Chiesi Clinical Trial Site

Troyan Municipality, 5600, Bulgaria

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Chiesi Clinical Trial Site

Varna, 1510, Bulgaria

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Chiesi Clinical Trial SIte

Varna, 9010, Bulgaria

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Chiesi Clinical Trial Site

Mělník, 27601, Czechia

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Chiesi Clinical Trial Site

Neratovice, 27711, Czechia

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Chiesi Clinical Trial Site

Prague, 14000, Czechia

Location

Chiesi Clinical trial

Marmande, 47200, France

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Chiesi Clinical Trial

Perpignan, 66000, France

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Chiesi Clinical Trial Site

Toulon, 83000, France

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Chiesi Clinical Trial Site

Berlin, 10117, Germany

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Chiesi Clinical Trial Site

Berlin, 12043, Germany

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Chiesi Clinical Trial Site

Bonn, 53119, Germany

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Chiesi Clinical Trial Site

Düren, 52349, Germany

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Chiesi Clinical Trial Site

Hamburg, 20251, Germany

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Chiesi Clinical Trial Site

Leipzig, 04207, Germany

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Chiesi Clinical Trial Site

Leipzig, 04357, Germany

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Chiesi Clinical Trial Site

Magdeburg, 39112, Germany

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Chiesi Clinical Trial Site

Radebeul, 01445, Germany

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Chiesi Clinical Trial Site

Saarbrücken, 66111, Germany

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Chiesi Clinical Trial Site

Schwabach, 91126, Germany

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Chiesi Clinica Trial Site

Witten, 58452, Germany

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Chiesi Clinical Trial Site

Budapest, H-1122, Hungary

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Chiesi Clinical Trial Site

Dabas, 2370, Hungary

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Chiesi Clinical Trial Site

Deszk, 6772, Hungary

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Chiesi Clinical Trial Site

Gödöllő, 21100, Hungary

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Chiesi Clinical Trial Site

Komárom, 2900, Hungary

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Chiesi Clinical Trial Site

Pécs, 7624, Hungary

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Chiesi Clinical Trial Site

Siófok, 8600, Hungary

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Chiesi Clinical Trial Site

Százhalombatta, 2440, Hungary

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Chiesi Clinical Trial Site

Szolnok, 5000, Hungary

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Chiesi Clinical Trial Site

Padua, 35013, Italy

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Chiesi Clinical Trial Site

Parma, 43125, Italy

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Chiesi Clinical Trial Site

Pisa, 56124, Italy

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Chiesi Clinical Trial Site

Pordenone, 323170, Italy

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Chiesi Clinical Trial Site

Verona, 37134, Italy

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Chiesi Clinical Trial Site

Bialystok, 15025, Poland

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Chiesi Clinical Trial Site

Bialystok, 15274, Poland

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Chiesi Clinical Trial Site

Bienkówka, 34200, Poland

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Chiesi Clinical Trial Site

Gdansk, 80847, Poland

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Chiesi Clinical Trial Site

Giżycko, 11500, Poland

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Chiesi Clinical Trial Site

Gmina Jędrzejów, 28300, Poland

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Chiesi Clinical Trial Site

Katowice, 40752, Poland

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Chiesi Clinical Trial Site

Katowice, 40952, Poland

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Chiesi Clinical Trial Site

Lodz, 90153, Poland

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Chiesi Clinical Trial Site

Lodz, 92107, Poland

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Chiesi Clinical Trial Site

Lublin, 20718, Poland

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Chiesi Clinical Trial Site

Ostróda, 14100, Poland

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Chiesi Clinical Trial Site

Ostrów Wielkopolski, 63400, Poland

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Chiesi Clinical Trial Site

Rzeszów, 35051, Poland

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Chiesi Clinical Trial Site

Moscow, 109147, Russia

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Chiesi Clinical Trial Site

Moscow, 117593, Russia

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Chiesi Clinical Trial Site

Saratov, 410000, Russia

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Chiesi Clinica Trial Site

Yaroslavl, 150030, Russia

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Chiesi Clinical Trial Site

Birmingham, B15 2SQ, United Kingdom

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Chiesi Clinical Trial Site

Chorley, PR7 7NA, United Kingdom

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Chiesi Clinical Trial Site

Manchester, M15 6SE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27938358 RESULT

Related Links

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

MeSH Terms

Conditions

Asthma

Interventions

Beclomethasone; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Clinical Trial INFO
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+39 0521 2791

Study Officials

• Pierluigi Paggiaro, MD, PhD

  Cardio-Thoracic and Vascular Dept, University of Pisa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2012
• First Posted: April 13, 2012
• Study Start: April 20, 2012
• Primary Completion: November 29, 2012
• Study Completion: November 29, 2012
• Last Updated: March 19, 2026
• Results First Posted: March 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5); FR (3); BU (13); CZ (3); PL (14); DE (12); RU (4); HU (9); GB (3)