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

Condition(s) targeted: Bronchial Asthma

Intervention: salbutamol 100 mcg (Drug); BDP/salbutamol HFA pMDI (Drug); BDP/salbutamol CFC pMDI (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Chiesi Farmaceutici S.p.A.

Official(s) and/or principal investigator(s):
Giovanni Cremonesi, M D, Study Director, Affiliation: Chiesi Farmaceutici S.p.A.
Gabriele Nicolini, CPM, Study Director, Affiliation: Chiesi Farmaceutici S.p.A.
Luis Puente, Dr, Principal Investigator, Affiliation: Hospital General Universitario Gregorio Maranon, Madrid
Giorgio Walter Canonica, Prof., Principal Investigator, Affiliation: Ospedale S.Martino e Cliniche Universitarie Convenzionate, Genova, Italy
Igor Bereznyakov, Prof., Principal Investigator, Affiliation: Department of therapy of Kharkov Academy of Postgraduate Education, Kharkov, Ukraine

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).

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Mean value of morning PEF (daily measured by the patient)

Secondary outcome:

Morning PEF daily measured by the patient at any other time point

Evening PEF, and morning and evening FEV1 daily measured by the patient

Pulmonary function parameters (FEV1, FVC, PEF and FEF25-75%)

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);

Rates of asthma exacerbations (in total and by severity)

Time to first asthma exacerbation

Night-time and daytime use of relief salbutamol, and number of days (both day and night) without intake of salbutamol

Nighttime and daytime symptoms scores, and number of symptoms-free days (both day and night)

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.

Minimum age: 18 Years. Maximum age: 64 Years. Gender(s): Both.

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.

Unità Operativa Complessa di Clinica fisiologica e Pneumologia - Dipartimento di Medicina Interna e Specialità Mediche (DI.MI.) - Ospedale S. Martino e Cliniche Universitarie Convenzionate, Genova 16129, Italy; Recruiting
Giorgio Walter Canonica, Prof., Phone: +39-0105553513, Email: gcanonica@qubisoft.it
Giorgio Walter Canonica, Prof., Principal Investigator

Unità Dipartimentale di Fisiopatologia Respiratoria -Dipartimento di Medicina Interna e Specialità Mediche (DI.MI.) - Ospedale S. Martino e Cliniche Universitarie Convenzionate, Genova 16129, Italy; Recruiting
Vito Brusasco, Prof., Phone: +39-0103537690, Email: Vito.Brusasco@unige.it
Vito Brusasco, Prof., Principal Investigator

Dipartimento di Medicina Ambientale e Sanità Pubblica-Sede di Medicina del Lavoro Servizio di Fisiopatologia Respiratoria, Padova 35127, Italy; Recruiting
Piero Maestrelli, Prof., Phone: +39-0498212541, Email: piero.maestrelli@unipd.it
Piero Maestrelli, Prof., Phone: +39-0498212541, Email: piero.maestrelli@unipd.it
Piero Maestrelli, Prof., Principal Investigator

Malattie dell'Apparato Respiratorio - Università degli Studi di Pisa Ospedale Cisanello, Pisa 56100, Italy; Recruiting
Pierluigi Paggiaro, Prof., Phone: 050-995266, Ext: +39, Email: ppaggiaro@qubisoft.it
Pierluigi Paggiaro, Prof., Principal Investigator

Central Clinical Hospital №1 OAO"RZD",Pulmonology Department, Moscow 125315, Russian Federation; Not yet recruiting
Sergey Evgenievich Mikhaylov, Dr, Phone: 495 151 35 41, Ext: +7, Email: serg.mikh@mail.ru
Sergey Evgenievich Mikhaylov, Dr, Principal Investigator

Regional Clinical Hospital, Department of Therapeutics of Post Graduate, Yaroslavl Medical Academy, Yaroslavl 150062, Russian Federation; Not yet recruiting
Oleg Anatolievich Khrustalev, Prof., Phone: 4852 24 80 16, Ext: +7, Email: khrust@yrh.yar.ru
.Oleg Anatolievich Khrustalev, Prof, Principal Investigator

Clinical Hospital № 8, Pulmonology Department, Yaroslavl 150030, Russian Federation; Not yet recruiting
Natalia Petrovna Shilkina, Prof., Phone: 4852 44 54 04, Ext: + 7, Email: kpvb@pochta.ru
Natalia Petrovna Shilkina, Prof., Principal Investigator

Clinical Hospital № 2, Pulmonology Department, Yaroslavl 150010, Russian Federation; Not yet recruiting
Alexander Leonidovich Khokhlov, Prof., Phone: 4852 46 09 35, Ext: +7, Email: alekskhokhlov@yandex.ru
Alexander Leonidovich Khokhlov, Prof., Principal Investigator

City Clinical Hospital № 61, Pulmonology Department, Moscow 119048, Russian Federation; Not yet recruiting
Alexander Semenovich Solomatin, Dr., Phone: 495 246 75 18, Ext: +7, Email: protosha@mail.ru
Alexander Semenovich Solomatin, Dr., Principal Investigator

Hospital General Universitario Gregorio Marañón, Madrid 28007, Spain; Not yet recruiting
Luis Puente, Dr., Phone: +34915868000, Email: lpuente@separ.es
Luis Puente, Dr., Principal Investigator

Hospital Central de la Defensa Gomez Ulla, Madrid 28047, Spain; Not yet recruiting
Javier Jareño, Dr., Phone: +34-914228000
Javier Jareño, Dr., Principal Investigator

Servicio de Neumologia Hospital Universitario La Paz, Madrid 28046, Spain; Not yet recruiting
Francisco Garcia-Rio, Dr., Phone: +34-917277000, Email: fgr01m@jazzfree.com
Francisco Garcia-Rio, Dr., Principal Investigator

Department of Therapy of Kharkov Medical Academy of Postgraduate Education City Multifield Clinical Hospital n° 25, Kharkov 61008, Ukraine; Recruiting
Igor G. Bereznyakov, Prof., Phone: 0572955947, Ext: +38
Igor G. Bereznyakov, Prof., Principal Investigator

Pulmonological Department of the Institute of Therapy Ukrainian Academy of Medical Science, Kharkov 61035, Ukraine; Recruiting
Vladimir Vyacheslavovivh Yefimov, Dr., Phone: 0577751551, Ext: + 38
Vladimir Vyacheslavovivh Yefimov, Dr., Principal Investigator

Pulmonological Department # 2 City Clinical Hospital # 13, Kharkov 61035, Ukraine; Recruiting
Victor Ivanovich Blazhko, Dr., Phone: 0577210948, Ext: +38
Victor Ivanovich Blazhko, Dr., Principal Investigator

Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine, Kiev 03680, Ukraine; Recruiting
Yuriy Ivanovich Feshchenko, Prof., Phone: 0442758328, Ext: +38
Yuriy Ivanovich Feshchenko, Prof., Principal Investigator

Department of General Practice - Family Medecine Medical Academy of post-graduate education. City Clinical Hospital N° 17, Kharkov 61037, Ukraine; Recruiting
Alexey. N. Korzh, Prof., Phone: 0577153421, Ext: +38
Alexey. N. Korzh, Prof., Principal Investigator

Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Disease of the Institute of Phtisiology and Pulmonology Academy of Medical Sciences of the Ukraine, Kiev 03680, Ukraine; Recruiting
Lyudmyla Aleksandrovna Yashyna, Prof., Phone: 0442750568, Ext: +38
Lyudmyla Aleksandrovna Yashyna, Prof., Principal Investigator

Institute of Phthisiology and Pulmonology Acedemy of Medical Science of the Ukraine, Kiev 03680, Ukraine; Recruiting
Viktoria Pavlovna Kostromina, Prof., Phone: 0442753602, Ext: +38
Viktoria Pavlovna Kostromina, Prof., Principal Investigator

Department of Hospital Therapy of Lugansk State Medical Institute, Lugansk 91045, Ukraine; Recruiting
Vladimir Ignatyevich Putintsev, Prof., Phone: 0642580979, Ext: +38
Vladimir Ignatyevich Putintsev, Prof., Principal Investigator

Department of Pediatrics and laboratory diagnostics, Dniepropetrovsk State Medical Academy City Clinical Hospital No. 8. Pulmonology Department. 55, Krivoi Rog 50082, Ukraine; Not yet recruiting
Mokia Serbina, prof, Phone: 0564 36 62 82, Ext: + 38, Email: dekan@alba.dp.ua
Mokia Serbina, Prof., Principal Investigator

Pulmonological and Allergological Department of the Kharkov Regional Clinical Hospital, Kharkov 61022,, Ukraine; Not yet recruiting
Semydotska, Prof., Phone: 057 705 0209, Ext: +38, Email: vade_mecum2001@yahoo.com
Semydotska, Prof., Principal Investigator

Department of propaedeutics of internal diseases #1. Kharkov State Medical University., Kharkov 61022, Ukraine; Not yet recruiting
Olga М Kovalyova, Prof., Phone: 057 732 33 44, Ext: +38, Email: svokov@ic.kharkov.ua
Olga М. Kovalyova, Prof., Principal Investigator

General Therapy Clinic Central Military Clinical Hospital of Ministry of Defenses of Ukraine, Kyiv 01133, Ukraine; Not yet recruiting
Sergiy S. Simonov, Dr., Phone: 044 529 26 21, Ext: +38, Email: ssimonov54@mail.ru
Sergiy S. Simonov, Dr., Principal Investigator

Central Military Hospital of North Region. Pulmonological Department, Kharkov 61022, Ukraine; Not yet recruiting
Svetlana Prof. Olshtynska, Phone: 057 702 49 64, Ext: +38, Email: nrv@nevod.nt.ua
Svetlana Olshtynska, Prof, Principal Investigator

Department of Hospital Therapy, Lviv State Medical University named by Danylo Galytsky, Lviv Regional Clinical Hospital, Lviv 79010, Ukraine; Not yet recruiting
Orest. O. Abrahamovych, Prof, Phone: 0322 76 97 63, Ext: +38, Email: docorest@sc.net.ua
Orest O. Abrahamovych, Prof., Principal Investigator

Servizio di Fisiopatologia Respiratoria Diagnostica Allergologica e Biologia Respiratoria Endoscopica e Toracica U.O.C. di Pneumologia Ospedale Orlandi, Bussolengo, (VR) 37012, Italy; Recruiting
Roberto Dal Negro, Dr., Phone: +39-0456769193, Email: rdalnegro@ulss22.ven.it
Roberto Dal Negro, Dr., Principal Investigator

Starting date: November 2007
Ending date: December 2008
Last updated: June 26, 2008