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Efficacy and Tolerability of Beclomethasone Plus Salbutamol in HFA pMDI Fixed Combination vs Beclomethasone Plus Salbutamol in CFC pMDI Fixed Combination in a 12-Week Treatment Period of Adult Patients With Uncontrolled Asthma
This study is currently recruiting participants.
Verified by Chiesi Farmaceutici S.p.A., June 2008
Sponsored by: Chiesi Farmaceutici S.p.A.
Information provided by: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT00528723
  Purpose

The purpose of this trial is to verify if the test treatment BDP 250 mcg/salbutamol 100 mcg HFA pMDI fixed combination is non-inferior to BDP 250 mcg/salbutamol 100 mcg pMDI fixed combination given with the conventional CFC propellant (Clenil® Compositum 250, Chiesi Farmaceutici) in terms of Pulmonary Function (morning PEF).


Condition Intervention Phase
Bronchial Asthma
Drug: salbutamol 100 mcg
Drug: BDP/salbutamol HFA pMDI
Drug: BDP/salbutamol CFC pMDI
Phase III

MedlinePlus related topics: Asthma
Drug Information available for: Albuterol sulfate Albuterol Levalbuterol hydrochloride Levalbuterol tartrate Beclomethasone dipropionate Beclomethasone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Multicentre, Multinational, Randomised, Double Blind, Double Dummy, Active Drug Controlled, Parallel Group Study Design Clinical Trial of the Efficacy and Tolerability of Beclomethasone Dipropionate 250 Mcg Plus Salbutamol 100 Mcg in HFA pMDI Fixed Combination vs. Beclomethasone Dipropionate 250 Mcg Plus Salbutamol 100 Mcg in CFC pMDI (Clenil® Compositum 250) Fixed Combination in a 12-Week Treatment Period of Adult Patients With Uncontrolled Asthma

Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • Mean value of morning PEF (daily measured by the patient) [ Time Frame: last 2 weeks treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Morning PEF daily measured by the patient at any other time point [ Time Frame: last 2 weeks treatment ] [ Designated as safety issue: No ]
  • Evening PEF, and morning and evening FEV1 daily measured by the patient [ Time Frame: all treatment period (12 weeks), at each two weeks ] [ Designated as safety issue: No ]
  • Pulmonary function parameters (FEV1, FVC, PEF and FEF25-75%) [ Time Frame: clinic visits ] [ Designated as safety issue: No ]
  • Changes from pre-dosing of pulmonary function parameters measured at in the interval 0-60 minutes (pre-dose and 5, 15, 30 and 60 minutes post-dose); [ Time Frame: baseline (visit 2) and end of treatment (visit 6) ] [ Designated as safety issue: No ]
  • Rates of asthma exacerbations (in total and by severity) [ Time Frame: all treatment period, at each two weeks ] [ Designated as safety issue: No ]
  • Time to first asthma exacerbation [ Time Frame: all treatment period, at each two weeks ] [ Designated as safety issue: No ]
  • Night-time and daytime use of relief salbutamol, and number of days (both day and night) without intake of salbutamol [ Time Frame: all treatment period, at each two weeks ] [ Designated as safety issue: No ]
  • Nighttime and daytime symptoms scores, and number of symptoms-free days (both day and night) [ Time Frame: all treatment period, at each two weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: November 2007
Estimated Study Completion Date: December 2008
Estimated Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
BDP/salbutamol HFA pMDI
Drug: salbutamol 100 mcg
To be used as needed for symptom relief
Drug: BDP/salbutamol HFA pMDI
Patients assigned to BDP/salbutamol HFA pMDI will receive 2 puffs twice daily (morning and evening), for a total daily dose of BDP 1000 mcg/salbutamol 400 mcg, plus 2 puffs twice daily of alternative CFC placebo
B: Active Comparator
BDP/salbutamol CFC pMDI
Drug: salbutamol 100 mcg
To be used as needed for symptom relief
Drug: BDP/salbutamol CFC pMDI
Patients assigned to BDP/salbutamol CFC pMDI will receive 2 puffs twice daily (morning and evening), for a total daily dose of BDP 1000 mcg/salbutamol 400 mcg, plus 2 puffs twice daily of alternative HFA placebo

Detailed Description:

Asthma is a chronic inflammatory disorder of the airways and a serious public health worldwide problem, affecting people of all ages, with an estimate of 300 millions affected individuals.When uncontrolled, asthma can place severe limits on daily life, and can sometimes be fatal.

There are two major classes of inhaled therapy for the treatment of reversible obstructive airways disease: antinflammatory agents and bronchodilators. In particular, BDP 250 mcg plus salbutamol 100 mcg in fixed combination is an effective and safe method to control symptoms of persistent asthma in adults.

This study has been designed to compare the efficacy, safety and tolerability of a new BDP 250 mcg/salbutamol 100 mcg HFA pMDI fixed combination with the same CFC-formulated fixed combination, which is on the market from some decades.The HFA propelled product is developed to replace the CFC formulation already marketed according to the European Union's Committee for Proprietary Medicinal Products (CPMP) Note for Guidance (III/5378/93 - Final) in order to prevent from depletion of stratospheric ozone.

The primary objective of this trial is to demonstrate that the test treatment BDP 250 mcg/salbutamol 100 mcg HFA pMDI fixed combination is non-inferior to BDP 250 mcg/salbutamol 100 mcg pMDI fixed combination given with the conventional CFC propellant (Clenil® Compositum 250, Chiesi Farmaceutici) in terms of Pulmonary Function (morning PEF).

Given the aim of the study, the population to be monitored includes adult patients with persistent asthma according to the current guidelines. The treatment period will be preceded by a 2-week run-in period. Subjects satisfying all the inclusion and exclusion criteria will then enter the 12-week treatment period. Clinic visits will take place at the start and end of the run-in period, and after 2, 4, 8 and 12 weeks after randomisation.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained,
  2. Male or female out-patients aged ³ 18 and < 65 years;
  3. Uncontrolled asthma defined according to the GINA 2006 "Classification of Levels of Asthma Control". This definition includes the presence of two or more of the following features (in addition to the required range of FEV1): a) daytime asthma symptoms > twice a week; b) any limitation of activities; c) any nocturnal symptoms/awakening; b) need for reliever/rescue treatment > twice a week. These conditions are to be based on recent medical history and are to be confirmed in the 2-week run-in period;
  4. Forced expiratory volume in the first second (FEV1) ³ 60% and < 80% of the predicted normal value;
  5. Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200 mL) from pre-bronchodilator value in the measurement of FEV1 30 minutes following 4 puffs (4 ´ 100 µg) of inhaled salbutamol administered via pMDI. The reversibility test can be avoided in patients having a documented positive response in the previous 6 months;
  6. Non-smokers or ex-smokers with a cumulative tobacco exposure less than 5 pack-years and who have stopped smoking since more than 1 year;
  7. A co-operative attitude and ability to be trained to correctly use the pMDIs;
  8. At the end of the 2-week run-in period, the condition of uncontrolled asthma (see inclusion criteria No. 3) is to be confirmed by reviewing the diary cards for run-in.

Exclusion Criteria:

  1. Inability to carry out pulmonary function testing;
  2. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD;
  3. History of near fatal asthma;
  4. Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks;
  5. Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months;
  6. Patients who have been treated with an inhaled corticosteroid in the previous 4 weeks;
  7. Patients who have been treated with nebulized, oral, intravenous or intramuscular corticosteroids in the past 8 weeks or depot injectable corticosteroids in the past 12 weeks;
  8. Patients who have been treated with a long-acting β2-agonist (LABA) in the past 2 weeks;
  9. Patients who have been treated with an oral β2-agonist in the past 48 hours;
  10. Patients who have been treated with a short-acting β2-agonist (SABA) in the past 6 hours;
  11. Patients who have been treated with nebulized bronchodilators in the past 2 weeks;
  12. Patients who have been treated with anticholinergic medications (by any route) in the past 2 weeks;
  13. Patients who have been treated with a xanthine derivative (by any route) in the past 4 weeks;
  14. Patients who have been treated with an inhaled cromone or a leukotriene modifier in the past 4 weeks;
  15. History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias;
  16. Diabetes mellitus;
  17. Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass graft (CABG) during the previous six months;
  18. Patients with an abnormal QTc interval value in the ECG test, defined as > 450 msec in males or > 470 msec in females;
  19. Patients with a serum potassium value ≤ 3.5 mEq/L (or 3.5 mmol/L) and/or fasting serum glucose value ≥ 140 mg/dL (or 7.77 mmol/L);
  20. Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree;
  21. Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases;
  22. Cancer or any chronic diseases with prognosis < 2 years;
  23. Pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization).
  24. History of alcohol or drug abuse;
  25. Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use;
  26. Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;
  27. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
  28. Patients who received any investigational new drug within the last 12 weeks;
  29. Patients who have been previously enrolled in this study;
  30. At the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of FEV1 measured at the clinics at the end of the run-in period ³ 15% in respect of the pre-bronchodilator value measured at the start of the run-in period;
  31. Patients with asthma exacerbations during the run-in period will also be excluded from the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00528723

Locations
Italy
Unità Operativa Complessa di Clinica fisiologica e Pneumologia - Dipartimento di Medicina Interna e Specialità Mediche (DI.MI.) - Ospedale S. Martino e Cliniche Universitarie Convenzionate Recruiting
Genova, Italy, 16129
Contact: Giorgio Walter Canonica, Prof.     +39-0105553513     gcanonica@qubisoft.it    
Principal Investigator: Giorgio Walter Canonica, Prof.            
Unità Dipartimentale di Fisiopatologia Respiratoria -Dipartimento di Medicina Interna e Specialità Mediche (DI.MI.) - Ospedale S. Martino e Cliniche Universitarie Convenzionate Recruiting
Genova, Italy, 16129
Contact: Vito Brusasco, Prof.     +39-0103537690     Vito.Brusasco@unige.it    
Principal Investigator: Vito Brusasco, Prof.            
Dipartimento di Medicina Ambientale e Sanità Pubblica-Sede di Medicina del Lavoro Servizio di Fisiopatologia Respiratoria Recruiting
Padova, Italy, 35127
Contact: Piero Maestrelli, Prof.     +39-0498212541     piero.maestrelli@unipd.it    
Contact: Piero Maestrelli, Prof.     +39-0498212541     piero.maestrelli@unipd.it    
Principal Investigator: Piero Maestrelli, Prof.            
Malattie dell'Apparato Respiratorio - Università degli Studi di Pisa Ospedale Cisanello Recruiting
Pisa, Italy, 56100
Contact: Pierluigi Paggiaro, Prof.     050-995266 ext +39     ppaggiaro@qubisoft.it    
Principal Investigator: Pierluigi Paggiaro, Prof.            
Italy, (VR)
Servizio di Fisiopatologia Respiratoria Diagnostica Allergologica e Biologia Respiratoria Endoscopica e Toracica U.O.C. di Pneumologia Ospedale Orlandi Recruiting
Bussolengo, (VR), Italy, 37012
Contact: Roberto Dal Negro, Dr.     +39-0456769193     rdalnegro@ulss22.ven.it    
Principal Investigator: Roberto Dal Negro, Dr.            
Russian Federation
Central Clinical Hospital №1 OAO"RZD",Pulmonology Department Not yet recruiting
Moscow, Russian Federation, 125315
Contact: Sergey Evgenievich Mikhaylov, Dr     495 151 35 41 ext +7     serg.mikh@mail.ru    
Principal Investigator: Sergey Evgenievich Mikhaylov, Dr            
Regional Clinical Hospital, Department of Therapeutics of Post Graduate, Yaroslavl Medical Academy Not yet recruiting
Yaroslavl, Russian Federation, 150062
Contact: Oleg Anatolievich Khrustalev, Prof.     4852 24 80 16 ext +7     khrust@yrh.yar.ru    
Principal Investigator: .Oleg Anatolievich Khrustalev, Prof            
Clinical Hospital № 8, Pulmonology Department Not yet recruiting
Yaroslavl, Russian Federation, 150030
Contact: Natalia Petrovna Shilkina, Prof.     4852 44 54 04 ext + 7     kpvb@pochta.ru    
Principal Investigator: Natalia Petrovna Shilkina, Prof.            
Clinical Hospital № 2, Pulmonology Department Not yet recruiting
Yaroslavl, Russian Federation, 150010
Contact: Alexander Leonidovich Khokhlov, Prof.     4852 46 09 35 ext +7     alekskhokhlov@yandex.ru    
Principal Investigator: Alexander Leonidovich Khokhlov, Prof.            
City Clinical Hospital № 61, Pulmonology Department Not yet recruiting
Moscow, Russian Federation, 119048
Contact: Alexander Semenovich Solomatin, Dr.     495 246 75 18 ext +7     protosha@mail.ru    
Principal Investigator: Alexander Semenovich Solomatin, Dr.            
Spain
Servicio de Neumologia Hospital Universitario La Paz Not yet recruiting
Madrid, Spain, 28046
Contact: Francisco Garcia-Rio, Dr.     +34-917277000     fgr01m@jazzfree.com    
Principal Investigator: Francisco Garcia-Rio, Dr.            
Hospital Central de la Defensa Gomez Ulla Not yet recruiting
Madrid, Spain, 28047
Contact: Javier Jareño, Dr.     +34-914228000        
Principal Investigator: Javier Jareño, Dr.            
Hospital General Universitario Gregorio Marañón Not yet recruiting
Madrid, Spain, 28007
Contact: Luis Puente, Dr.     +34915868000     lpuente@separ.es    
Principal Investigator: Luis Puente, Dr.            
Ukraine
Department of Hospital Therapy, Lviv State Medical University named by Danylo Galytsky, Lviv Regional Clinical Hospital Not yet recruiting
Lviv, Ukraine, 79010
Contact: Orest. O. Abrahamovych, Prof     0322 76 97 63 ext +38     docorest@sc.net.ua    
Principal Investigator: Orest O. Abrahamovych, Prof.            
Pulmonological Department of the Institute of Therapy Ukrainian Academy of Medical Science Recruiting
Kharkov, Ukraine, 61035
Contact: Vladimir Vyacheslavovivh Yefimov, Dr.     0577751551 ext + 38        
Principal Investigator: Vladimir Vyacheslavovivh Yefimov, Dr.            
Pulmonological Department # 2 City Clinical Hospital # 13 Recruiting
Kharkov, Ukraine, 61035
Contact: Victor Ivanovich Blazhko, Dr.     0577210948 ext +38        
Principal Investigator: Victor Ivanovich Blazhko, Dr.            
Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine Recruiting
Kiev, Ukraine, 03680
Contact: Yuriy Ivanovich Feshchenko, Prof.     0442758328 ext +38        
Principal Investigator: Yuriy Ivanovich Feshchenko, Prof.            
Department of General Practice - Family Medecine Medical Academy of post-graduate education. City Clinical Hospital N° 17 Recruiting
Kharkov, Ukraine, 61037
Contact: Alexey. N. Korzh, Prof.     0577153421 ext +38        
Principal Investigator: Alexey. N. Korzh, Prof.            
Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Disease of the Institute of Phtisiology and Pulmonology Academy of Medical Sciences of the Ukraine Recruiting
Kiev, Ukraine, 03680
Contact: Lyudmyla Aleksandrovna Yashyna, Prof.     0442750568 ext +38        
Principal Investigator: Lyudmyla Aleksandrovna Yashyna, Prof.            
Institute of Phthisiology and Pulmonology Acedemy of Medical Science of the Ukraine Recruiting
Kiev, Ukraine, 03680
Contact: Viktoria Pavlovna Kostromina, Prof.     0442753602 ext +38        
Principal Investigator: Viktoria Pavlovna Kostromina, Prof.            
Department of Hospital Therapy of Lugansk State Medical Institute Recruiting
Lugansk, Ukraine, 91045
Contact: Vladimir Ignatyevich Putintsev, Prof.     0642580979 ext +38        
Principal Investigator: Vladimir Ignatyevich Putintsev, Prof.            
Department of Pediatrics and laboratory diagnostics, Dniepropetrovsk State Medical Academy City Clinical Hospital No. 8. Pulmonology Department. 55 Not yet recruiting
Krivoi Rog, Ukraine, 50082
Contact: Mokia Serbina, prof     0564 36 62 82 ext + 38     dekan@alba.dp.ua    
Principal Investigator: Mokia Serbina, Prof.            
Pulmonological and Allergological Department of the Kharkov Regional Clinical Hospital Not yet recruiting
Kharkov, Ukraine, 61022,
Contact: Semydotska, Prof.     057 705 0209 ext +38     vade_mecum2001@yahoo.com    
Principal Investigator: Semydotska, Prof.            
Department of propaedeutics of internal diseases #1. Kharkov State Medical University. Not yet recruiting
Kharkov, Ukraine, 61022
Contact: Olga М Kovalyova, Prof.     057 732 33 44 ext +38     svokov@ic.kharkov.ua    
Principal Investigator: Olga М. Kovalyova, Prof.            
General Therapy Clinic Central Military Clinical Hospital of Ministry of Defenses of Ukraine Not yet recruiting
Kyiv, Ukraine, 01133
Contact: Sergiy S. Simonov, Dr.     044 529 26 21 ext +38     ssimonov54@mail.ru    
Principal Investigator: Sergiy S. Simonov, Dr.            
Central Military Hospital of North Region. Pulmonological Department Not yet recruiting
Kharkov, Ukraine, 61022
Contact: Svetlana Prof. Olshtynska     057 702 49 64 ext +38     nrv@nevod.nt.ua    
Principal Investigator: Svetlana Olshtynska, Prof            
Department of Therapy of Kharkov Medical Academy of Postgraduate Education City Multifield Clinical Hospital n° 25 Recruiting
Kharkov, Ukraine, 61008
Contact: Igor G. Bereznyakov, Prof.     0572955947 ext +38        
Principal Investigator: Igor G. Bereznyakov, Prof.            
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
Study Director: Giovanni Cremonesi, M D Chiesi Farmaceutici S.p.A.
Study Director: Gabriele Nicolini, CPM Chiesi Farmaceutici S.p.A.
Principal Investigator: Luis Puente, Dr Hospital General Universitario Gregorio Maranon, Madrid
Principal Investigator: Giorgio Walter Canonica, Prof. Ospedale S.Martino e Cliniche Universitarie Convenzionate, Genova, Italy
Principal Investigator: Igor Bereznyakov, Prof. Department of therapy of Kharkov Academy of Postgraduate Education, Kharkov, Ukraine
  More Information

Responsible Party: Chiesi Farmaceutici ( Nicolini Gabriele )
Study ID Numbers: MC/PR/033004/002/06
Study First Received: September 11, 2007
Last Updated: June 26, 2008
ClinicalTrials.gov Identifier: NCT00528723  
Health Authority: Italy: Ministry of Health;   Ukraine: Ministry of Health;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Spain: Ministry of Health and Consumption

Keywords provided by Chiesi Farmaceutici S.p.A.:
beclomethasone
as needed
salbutamol
wheezing

Study placed in the following topic categories:
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Lung Diseases
Albuterol
Hypersensitivity, Immediate
Beclomethasone
Asthma
Respiratory Hypersensitivity

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Respiratory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Bronchial Diseases
Immune System Diseases
Adrenergic beta-Agonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Reproductive Control Agents
Hormones
Glucocorticoids
Adrenergic Agonists
Pharmacologic Actions
Tocolytic Agents
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Bronchodilator Agents

ClinicalTrials.gov processed this record on January 15, 2009