Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate Plus Formoterol vs Fluticasone Propionate Plus Salmeterol in the 6 Months Step Down Treatment of Asthma

Condition(s) targeted: Asthma

Intervention: Beclomethasone plus formoterol fixed combination (Drug); Fluticasone plus salmeterol fixed combination (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Chiesi Farmaceutici S.p.A.

Official(s) and/or principal investigator(s):
Pierluigi Paggiaro, MD, Principal Investigator, Affiliation: Ospedale Cisanello, Pisa

Overall contact:
Pierluigi Paggiaro, MD, Phone: 050995366

Asthma is a serious global health problem. People of all ages in countries throughout the world are affected by this chronic airway disorder that can be severe and sometimes fatal. The prevalence of asthma is increasing everywhere, especially among children. According to international guidelines, once control of asthma is achieved and maintained for at least 3 months, a gradual reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control. This will help reduce the risk of side effects and enhance patient adherence to the treatment plan.

Reduction of therapy in patients on combination therapy should begin with a reduction in the dose of inhaled glucocorticosteroid. 1 The present study is designed to evaluate if patients with controlled asthma treated with FP 1000 mcg + salmeterol 100 mcg daily can be stepped down. Stepping-down will be attempted with two medications: a new combination of extrafine beclomethasone dipropionate 400 mcg + formoterol 24 mcg daily (test medication, Foster™) and, alternatively, fluticasone propionate 500 mcg + salmeterol 100 mcg daily(reference medication) without losing asthma control. If this hypothesis will be confirmed, the present study will demonstrate that asthma control can be maintained with less than half the dose of inhaled corticosteroid and with less medical costs.

Given the aims of this study, the population to be monitored includes adult patients with moderate persistent asthma, which can be defined controlled according to the current guidelines under standard stabilised treatment. The intended treatment duration is therefore designed to ensure that good control of asthma is firmly achieved before stepping down the treatment (8 weeks run-in period), but also that the condition of the patients are followed long enough (24 weeks comparative treatment period) to ensure that a new stable condition is also obtained and properly monitored.

Official title: Prospective, Randomised, Open-Label, Multicentre, Active Drug Controlled, Parallel Group Design Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate 400 Mcg + Formoterol 24 Mcg pMDI Via HFA-134a (Foster™) vs. Fluticasone Propionate 500 Mcg + Salmeterol Xinafoate 100 Mcg DPI (Seretide Diskus®) in the 6 Months Stepdown Treatment of Adult Patients With Controlled Asthma

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Morning pre-dose PEF measured daily by patients (mean of the last 2 weeks of treatment period).

Secondary outcome:

symptom scores and symptom free days

morning and evening pre-dose PEF and FEV1 measured daily by patients;

pulmonary function tests measured at clinics (pre-dose PEF, FVC and FEV1);

change of FEV1 from pre-dose to 5, 15, 30 and 60 minutes post-dose;

number, frequency and severity of exacerbations, time to first exacerbation

adverse events and adverse drug reactions

use of relief salbutamol and days without use of relief salbutamol;

proportion of patients with controlled asthma and partly controlled asthma, weeks of controlled asthma and partly controlled asthma;

pharmaco-economic analysis of medical and non medical costs.

12 h-overnight urinary cortisol/creatinine

vital signs

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients will be enrolled for screening at Visit 1 into the run-in period if they

meet all the following criteria:

- Clinical diagnosis of moderate persistent asthma for at least 6 months, according to

GINA revised version 2005 guidelines 1 and considering current treatment;

- Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ≥ 80% of the

predicted normal value;

- Treated with fluticasone 1000 mcg + salmeterol 100 mcg daily for at least 4 weeks at

a stable dose;

- Reporting no nocturnal symptoms or awakenings, no exacerbations, no limitations of

activities, symptoms in ≤2 days and use of rescue medication ≤2 days per week, in the last 4 weeks;

- Exhibiting a co-operative attitude and ability to be trained to correctly use the

study devices and to complete the diary cards.

At the end of run in period (Week 8+0; Visit 3), patients will be recruited into the treatment period and randomized to treatment if they meet the following criterion:

- Asthma is controlled 1 in each of the last 4 weeks of run-in (no nocturnal symptoms

or awakenings; no exacerbations; no limitations of activities; symptoms in ≤2 days; use of rescue medication ≤2 days; morning PEF ≥80% of predicted in every day) confirmed by reviewing the diary cards.

Exclusion Criteria:

- Inability to carry out pulmonary function testing;

- Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the

NHLBI/WHO's GOLD guidelines;

- Current smokers or recent (less than one year) ex-smokers with a smoking history of

≥10 pack/years;

- History of near fatal asthma;

- Evidence of symptomatic infection of the airways in the previous 8 weeks;

- Three or more courses of oral corticosteroids or hospitalisation due to asthma during

the previous 6 months;

- Patients treated with anticholinergics and antihistamines during the previous 2

weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks;

- History or current evidence of heart failure, coronary artery disease, myocardial

infarction, severe hypertension, cardiac arrhythmias;

- Diabetes mellitus;

- PTCA or CABG during the previous six months;

- Patients with an abnormal QTc interval value in the ECG test, defined as >450 msec in

males or > 470 msec in females;

- 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;

- 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;

- Cancer or any chronic diseases with prognosis <2 years;

- History of alcohol or drug abuse;

- Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or

beta-blockers as regular use;

- Allergy, sensitivity or intolerance to study drugs and/or study drug formulation

ingredients;

- Patients who received any investigational new drug within the last 12 weeks;

At the end of run in period (Week 8+0; Visit 3), patients will not be randomized to treatment if they do not completely meet the definition of "controlled asthma". These subjects will be considered screening failures and will not count against the planned number to be recruited.

Pierluigi Paggiaro, MD, Phone: 050995366

Clinic of Pulmonology, University Hospital "Lozenetz", Sofia, Bulgaria; Not yet recruiting
Georgi Hinkov, Dr., Phone: 00359 2 960 7557, Email: drhinkov@abv.bg

Clinic of Pulmonology, UMHAT "Sveti Georgi", Plovdiv 4002, Bulgaria; Not yet recruiting
Vladimir Hodzhev, Prof, Phone: 0035932 602990, Email: vahodgev@abv.bg

First Internal Clinic, Endocrinology and Pulmonology Department MHAT, Stara Zagora 6000, Bulgaria; Not yet recruiting
Dimo Mitev Dimov, Dr, Phone: 00359 42 66 44 93, Email: dmdimov@yahoo.com

First Department of Pulmonology, Regional Dispensery of Pulmonology and Phtisiatric Diseases with Stationary (RDPPDS), Ruse 7002, Bulgaria; Not yet recruiting
Hristo Metev, Dr, Phone: 00359 82 82 38 79, Email: h_metev_2003@yahoo.com

U.O.C. S.Anna e S. Sebastiano - Malattie dell'apparato respiratorio, Caserta, Italy; Recruiting
MD
Riccardo Cioffi, MD, Principal Investigator

Ospedale S. Camillo de Lellis - U.O.C. Pneumologia, Chieti, Italy; Recruiting
Fernando De Benedetto, MD, Principal Investigator

Ospedale Cardarelli - Fisiopatologia Respiratoria, Napoli, Italy; Recruiting
Fausto De Michele, MD, Principal Investigator

CNR - Dipartimento di Fisiopatologia Respiratoria, Palermo, Italy; Recruiting
Mark Gjomarkaj, MD, Principal Investigator

Pulmonological Department of the Institute of Therapy, Ukrainian Academy of Medical Sciences, Kharkiv 61035, Ukraine; Not yet recruiting
Yefimov Volodymyr, Dr., Phone: +38 057 775 15 51, Email: igs@therapy.ac.kharkov.ua

Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine, Kiev 03680, Ukraine; Not yet recruiting
Feshchenko Yuriy, Prof., Phone: +380442750402, Email: admin@ifp.kiev.ua

Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases of the Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine, Kiev 03680, Ukraine; Not yet recruiting
Lyudmyla Yashyna, Prof., Phone: +38 044 275 0568, Email: diagnost@ifp.kiev.ua

Institute of pthysiology and pulmonology Academy of medical science of the Ukraine., Kiev 03680, Ukraine; Not yet recruiting
Viktoria Kostromina, Prof., Phone: +38 044 275 3602, Email: child@ifp.kiev.ua

Department of Hospital Therapy of Lugansk State Medical Institute. Lugansk Regional Clinical Hospital, Lugansk 91045, Ukraine; Not yet recruiting
Olena Olenitskaya, Dr., Phone: +380642580979

Department of General Practice- Family medicine. Medical Academy of postgraduate education., Kharkov, Ukraine; Not yet recruiting
Olexiy Korzh, Prof., Phone: + 38 057 738 70 18, Email: alexeykorzh@mail.ru

Pulmonological Department #2, Kharkiv 61035, Ukraine; Not yet recruiting
Dr. Viktor Blazhko, Phone: +38 057 721 09 48, Email: blazhkopulm@mail.ru

Department of Hospital Pediatrics Crimean State Medical University. Pulmonology Department of Republican Clinical Children's Hospital, Crimea 95004, Ukraine; Not yet recruiting
T. Kobets, Prof., Phone: + 38 0652 25 34 26, Email: kobez@yandex.ru

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

Clinical Hospital 8, Department of pediatrics and clinical laboratories, Kriviy Rig, Ukraine; Not yet recruiting
Svitlana Mokia-Serbina, Prof., Phone: +380564365303, Email: litvinova_2008@ukr.net

Starting date: April 2007
Ending date: July 2010
Last updated: January 20, 2009