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

Original Study ID : MC/PR/033011/005/06

NCT ID : NCT00497237

Brief Title : 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

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

Brief Summary :

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.

Source : Chiesi Farmaceutici S.p.A.

Overall Status : Recruiting

Start Date : April 2007

End Date : July 2010

Completion Date : July 2010

Official Title : Phase 3

Phase : Interventional

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

Enrollment : 382

Verification Date : January 2009

First Received Date : July 4, 2007

Trial Eligibility

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.

Gender : Both

Minimum Age : 18 Years

Maximum Age : 65 Years

Healthy Volunteers : No

Facilities

Facility Name : Clinic of Pulmonology, University Hospital "Lozenetz"

Status : Not yet recruiting

City : Sofia

Country : Bulgaria

Facility Name : Clinic of Pulmonology, UMHAT "Sveti Georgi"

Status : Not yet recruiting

City : Plovdiv

Zip Code : 4002

Country : Bulgaria

Facility Name : First Internal Clinic, Endocrinology and Pulmonology Department MHAT

Status : Not yet recruiting

City : Stara Zagora

Zip Code : 6000

Country : Bulgaria

Facility Name : First Department of Pulmonology, Regional Dispensery of Pulmonology and Phtisiatric Diseases with Stationary (RDPPDS)

Status : Not yet recruiting

City : Ruse

Zip Code : 7002

Country : Bulgaria

Facility Name : U.O.C. S.Anna e S. Sebastiano - Malattie dell'apparato respiratorio

Status : Recruiting

City : Caserta

Zip Code : 7002

Country : Italy

Facility Name : Ospedale S. Camillo de Lellis - U.O.C. Pneumologia

Status : Recruiting

City : Chieti

Zip Code : 7002

Country : Italy

Facility Name : Ospedale Cardarelli - Fisiopatologia Respiratoria

Status : Recruiting

City : Napoli

Zip Code : 7002

Country : Italy

Facility Name : CNR - Dipartimento di Fisiopatologia Respiratoria

Status : Recruiting

City : Palermo

Zip Code : 7002

Country : Italy

Facility Name : Pulmonological Department of the Institute of Therapy, Ukrainian Academy of Medical Sciences

Status : Not yet recruiting

City : Kharkiv

Zip Code : 61035

Country : Ukraine

Facility Name : Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine

Status : Not yet recruiting

City : Kiev

Zip Code : 03680

Country : Ukraine

Facility Name : Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases of the Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine

Status : Not yet recruiting

City : Kiev

Zip Code : 03680

Country : Ukraine

Facility Name : Institute of pthysiology and pulmonology Academy of medical science of the Ukraine.

Status : Not yet recruiting

City : Kiev

Zip Code : 03680

Country : Ukraine

Facility Name : Department of Hospital Therapy of Lugansk State Medical Institute. Lugansk Regional Clinical Hospital

Status : Not yet recruiting

City : Lugansk

Zip Code : 91045

Country : Ukraine

Facility Name : Department of General Practice- Family medicine. Medical Academy of postgraduate education.

Status : Not yet recruiting

City : Kharkov

Zip Code : 91045

Country : Ukraine

Facility Name : Pulmonological Department #2

Status : Not yet recruiting

City : Kharkiv

Zip Code : 61035

Country : Ukraine

Facility Name : Department of Hospital Pediatrics Crimean State Medical University. Pulmonology Department of Republican Clinical Children's Hospital

Status : Not yet recruiting

City : Crimea

Zip Code : 95004

Country : Ukraine

Facility Name : Pulmonological and Allergological Department of the Kharkov Regional Clinical Hospital

Status : Not yet recruiting

City : Kharkov

Zip Code : 61022

Country : Ukraine

Facility Name : Clinical Hospital 8, Department of pediatrics and clinical laboratories

Status : Not yet recruiting

City : Kriviy Rig

Zip Code : 61022

Country : Ukraine

OutComes

Primary OutComes

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

Time Frame : mean of the last 2 weeks of treatment period

Safety issue : No

Secondary OutComes

Measure : symptom scores and symptom free days

Time Frame : in the whole study period and every 2-week period

Safety issue : No

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

Time Frame : daily and mean each 2-week period

Safety issue : No

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

Time Frame : at aech clinic visit

Safety issue : No

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

Time Frame : randomization visit and end of treatment visit

Safety issue : No

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

Time Frame : whole study period

Safety issue : No

Measure : adverse events and adverse drug reactions

Time Frame : retrospectively assessed at each visit

Safety issue : Yes

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

Time Frame : daily

Safety issue : No

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

Time Frame : weekly

Safety issue : No

Measure : pharmaco-economic analysis of medical and non medical costs.

Time Frame : during study period

Safety issue : No

Measure : 12 h-overnight urinary cortisol/creatinine

Time Frame : (collected at visit 3, 6 and 9)

Safety issue : Yes

Measure : vital signs

Time Frame : at each visit

Safety issue : Yes

Interventions

Type : Drug

Name : Beclomethasone plus formoterol fixed combination

Description : 100+6 pMDI

Type : Drug

Name : Fluticasone plus salmeterol fixed combination

Description : diskus 250/50

Clinical Trial Name - Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate Plus Formoterol vs Flutic