EVALUATION OF CARDIAC SAFETY, TOLERABILITY AND EFFICACY OF CUMULATIVE DOSES OF CHF5188 pMDI (FIXED COMBINATION BUDESONIDE/CARMOTEROL 200/1 µg) COMPARED TO SAME CUMULATIVE DOSES OF CARMOTEROL pMDI AND PLACEBO IN ASTHMATIC PATIENTS A MONOCENTER, RANDOMISED, DOUBLE-BLIND, 3-WAY, CROSS-OVER CLINICAL STUDY

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-000774-23-GB
• Date of registration: 26/04/2011
• Prospective Registration: No
• Primary sponsor: Chiesi Farmaceutici S.p.A
• Public title: EVALUATION OF CARDIAC SAFETY, TOLERABILITY AND EFFICACY OF CUMULATIVE DOSES OF CHF5188 pMDI (FIXED COMBINATION BUDESONIDE/CARMOTEROL 200/1 µg) COMPARED TO SAME CUMULATIVE DOSES OF CARMOTEROL pMDI AND PLACEBO IN ASTHMATIC PATIENTS A MONOCENTER, RANDOMISED, DOUBLE-BLIND, 3-WAY, CROSS-OVER CLINICAL STUDY
• Scientific title: EVALUATION OF CARDIAC SAFETY, TOLERABILITY AND EFFICACY OF CUMULATIVE DOSES OF CHF5188 pMDI (FIXED COMBINATION BUDESONIDE/CARMOTEROL 200/1 µg) COMPARED TO SAME CUMULATIVE DOSES OF CARMOTEROL pMDI AND PLACEBO IN ASTHMATIC PATIENTS A MONOCENTER, RANDOMISED, DOUBLE-BLIND, 3-WAY, CROSS-OVER CLINICAL STUDY
• Date of first enrolment: 10/05/2007
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000774-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
· Written informed consent obtained;
· Male or female patients aged = 18 and < 70 years;
· Patients with a clinical diagnosis of persistent asthma according to the GINA 2005 “Classification of Asthma Severity by Daily Medication Regimen and Response to Treatment”;
· Patients already treated with inhaled corticosteroids at a stable dose for at least 4 weeks prior to inclusion;
. Patients with forced expiratory volume in the first second (FEV1) less or equal to 90% of predicted for the patient normal value and not less than 0.9 L in absolute value;
· Patients with a documented positive response to the reversibility test, defined as ?FEV1 = 15% and = 200 mL over baseline, 30 minutes after 200 µg salbutamol pMDI;
· Patients with normal blood pressure (i.e. supine SBP = 140 mmHg, supine DBP = 90 mmHg);
· Patients with normal ECG with heart rate < 100 bpm and QTcB interval = 450msec for males and = 470msec for females;
· Patients with a co-operative attitude and ability to be trained to correctly use the pMDI.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will not be enrolled at Visit 1 into the run-in period if they meet any of the following criteria:
· Inability to carry out pulmonary function testing;
· Diagnosis of COPD as defined by the current GOLD guidelines;
· Current smoker or ex-smoker with total cumulative exposure equal or more than 5 pack-years and/or having stopped smoking one year or less prior to study start;
· History of near fatal asthma;
· Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks (e.g. oral corticosteroids intake);
· Patients presenting with 3 or more asthma exacerbations in the previous year;
· Hospitalisation due to asthma during the previous 8 weeks;
· Patients treated with oral or intravenous corticosteroids in the past 4 weeks or depot injectable corticosteroids in the past 8 weeks;
· Patients treated with short-acting ß2-agonists in the past 8 hours, long-acting ß2-agonists in the past 48 hours, short-acting anticholinergics in the past 12 hours, long-acting anticholinergics (i.e. tiotropium bromide) in the past 48 hours, leukotriene antagonists in the past 2 weeks;
· Patients treated with Duovent® and Berodual® in the past 12 hours;
· Patients treated with an inhaled combination drug (eg Seretide®, Symbicort®) in the past 48 hours;
· Patients who have changed their dose or formulation of inhaled corticosteroids during the previous 4 weeks;
· History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiovascular disease;
· Patients presenting with a clinically significant abnormality at a 12-lead ECG;
· Patients presenting with serum potassium < 3.5 mmol/L or > 6.0 mmol/L;
· Patients presenting with fasting blood glucose > 8 mmol/L;
· Clinically significant or unstable concomitant disease,
· Cancer or any other chronic disease with poor prognosis and /or affecting patient status;
· Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method. A pregnancy test will be performed at screening in women of childbearing potential;
· History of alcohol or drug abuse;
· Allergy, sensitivity or intolerance to beta2-aderenergic agonists and/or study drug formulation ingredients;
· Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
· Patients who received any investigational new drug within the last 8 weeks.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stable persistent asthma
MedDRA version: 13.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: CHF 5188 pMDI
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: Budesonide
CAS Number: 51333223
Current Sponsor code: CHF 1536
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Carmoterol hydrochloride
CAS Number: 137888-11-0
Current Sponsor code: CHF 4226.01
Other descriptive name: TA-2005
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Product Name: CHF 4226 pMDI
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: Carmoterol hydrochloride
CAS Number: 137888-11-0
Current Sponsor code: CHF 4226.01
Other descriptive name: TA-2005
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Primary end point(s): · QTcB interval (change from pre-dose to 6 hours after the last cumulative dose)
· FEV1 (% change from pre-dose to 120 min after the last cumulative dose).

Secondary Objective: To evaluate the safety and tolerability of CHF 5188 given in cumulative doses.

Main Objective: To establish the cardiac safety (QTcB interval) and the efficacy (FEV1) of cumulative-doses of CHF 5188.

Secondary ID(s)

CCD-0701-PR-0020