EVALUATION OF THE EFFECT OF 4 WEEKS TREATMENT WITH CHF 4226 pMDI 2µg DOSE GIVEN ONCE DAILY IN THE EVENING ON 24-HOUR TROUGH FEV1 IN ADULT AND ADOLESCENT PATIENTS AGED 15 YEARS OR OVER WITH MODERATE OR SEVERE PERSISTANT ASTHMA. A MULTICENTER, DOUBLE-BLIND, DOUBLE-DUMMY, RANDOMISED, PARALLEL GROUP, PLACEBO AND ACTIVE (FORMOTEROL 12µg B.I.D.) CONTROLLED, EFFICACY, SAFETY AND TOLERABILITY STUDY.

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2006-005689-38-GB
• Date of registration: 19/10/2011
• Prospective Registration: No
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: EVALUATION OF THE EFFECT OF 4 WEEKS TREATMENT WITH CHF 4226 pMDI 2µg DOSE GIVEN ONCE DAILY IN THE EVENING ON 24-HOUR TROUGH FEV1 IN ADULT AND ADOLESCENT PATIENTS AGED 15 YEARS OR OVER WITH MODERATE OR SEVERE PERSISTANT ASTHMA. A MULTICENTER, DOUBLE-BLIND, DOUBLE-DUMMY, RANDOMISED, PARALLEL GROUP, PLACEBO AND ACTIVE (FORMOTEROL 12µg B.I.D.) CONTROLLED, EFFICACY, SAFETY AND TOLERABILITY STUDY.
• Scientific title: EVALUATION OF THE EFFECT OF 4 WEEKS TREATMENT WITH CHF 4226 pMDI 2µg DOSE GIVEN ONCE DAILY IN THE EVENING ON 24-HOUR TROUGH FEV1 IN ADULT AND ADOLESCENT PATIENTS AGED 15 YEARS OR OVER WITH MODERATE OR SEVERE PERSISTANT ASTHMA. A MULTICENTER, DOUBLE-BLIND, DOUBLE-DUMMY, RANDOMISED, PARALLEL GROUP, PLACEBO AND ACTIVE (FORMOTEROL 12µg B.I.D.) CONTROLLED, EFFICACY, SAFETY AND TOLERABILITY STUDY.
• Date of first enrolment: 29/12/2006
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005689-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other:
• Phase: Human pharmacology (Phase I): Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): Therapeutic use (Phase IV):

Countries of recruitment

Bulgaria, Hungary, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients will be enrolled at Visit 1 into the run-in period if they meet all the following criteria: Written informed consent obtained; Male or female patients aged 15 years and over; Moderate or severe persistent asthma according to the GINA 2005 “Classification of Asthma Severity by Daily Medication Regimen and Response to Treatment”; Patients free of long-acting ß2 agonists treatment (LABAs) at least for 4 weeks before the screening visit and already treated for at least 1 month with inhaled corticosteroids at a stable dose corresponding to mild-medium asthma severity (GINA 2005) (up to 1000 µg BDP CFC or equivalent); Level of asthma control on existing therapy, defined as presence of day-time asthma symptoms > once a week and nocturnal asthma symptoms > twice a month. These findings are to be based on recent medical history and are to be confirmed at the end of the run-in period; 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; Positive response to the reversibility test in the screening visit, defined as an increase of at least 12% and at least 250 mL from pre-dosing value in the measurement of FEV1 30 minutes following 2 puffs (2 x 100 µg) of inhaled salbutamol pMDI; Non-smokers or ex-smokers < 5 pack-year [e.g. less than 1 pack cigarettes (i.e. 20 cigarettes) per day for 5 years or 2 packs cigarettes per day for 2.5 years] and having stopped smoking > 1 year; A co-operative attitude and ability to be trained to correctly use the pMDI and the Aerolizer® inhaler; At the end of the run-in period, the presence of day-time asthma symptoms > once a week (but not every day) and nocturnal asthma symptoms > twice a month is to be confirmed by means of patient interview by the investigator.
Are the trial subjects under 18? yes
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 or of a past hospitalisation for asthma in an intensive care unit; History of significant seasonal variation of asthma; Evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 4 weeks (e.g. oral corticosteroids intake); 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, short-acting anticholinergics in the past 12 hours, long-acting anticholinergics (i.e. tiotropium bromide) in the past 48 hours, leukotriene modifiers in the past 2 weeks; Patients treated with oral or nebulized bronchodilators in the 4 weeks prior to study start; Patients treated with nebulized corticosteroids in the 4 weeks prior to study start; Patients who have changed their dose or formulation of inhaled or nasal corticosteroids during the previous 4 weeks; Patients treated with fixed combination of inhaled corticosteroids and ß2-agonists (e.g. Seretide®, Symbicort®) during the previous 4 weeks prior to study start; Patients undergoing immunotherapy; Patients treated with a xanthine derivative (e.g. theophylline) any formulation in the 4 weeks prior to study start; Patients treated with sodium cromoglycate or nedocromil sodium in the 4 weeks prior to study start; History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe uncontrolled hypertension, cardiac arrhythmias or any other significant cardiac disease; Patients with a QTc interval (Bazett’s formula) in the ECG test > 450 msec in males or > 470 msec in females; Serum potassium < 3.5 mmol/L or > 6.0mmol/L; Clinically significant or unstable concurrent disease, e.g. uncontrolled diabetes mellitus; uncontrolled hyperthyroidism, significant hepatic impairment, significant pulmonary disease other than asthma (e.g. tuberculosis, lung cancer), gastrointestinal disease (e.g. active peptic ulcer), neurological or haematological autoimmune disorders; 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 (oral contraception, IUD, tubal ligature, double barrier method). A pregnancy test will be performed at screening in women of childbearing potential; History of alcohol or drug abuse; Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers; Allergy, sensitivity or intolerance to beta2-adrenergic 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

Persistent asthma
MedDRA version: 14.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: CHF 4226 1 µg - pMDI
Product Code: CHF 4226 HFA
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: Carmoterol Hydrochloride
CAS Number: 137888-11-0
Current Sponsor code: CHF 4226
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

Trade Name: FORADIL
Product Name: Foradil
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Formoterol Fumarate
CAS Number: 43229-80-7
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Trough FEV1 (L) (mean of 23 and 24 hours) at Day 28 (Visit 6) after 4 weeks of dosing.

Secondary Objective: - to compare the mean trough 23-24h FEV1 observed with CHF 4226 2 mcg q.d. with the one observed with formoterol 12 mcg bid after 4 weeks of dosing; - to compare the average (AUC standardised for time) FEV1, FVC, FEF25-75 0-3h post evening dose administration and the peak FEV1, FVC, FEF25-75 observed with CHF 4226 with the one observed with placebo and formoterol after the first dose, 1 day, 7 days, 14 days and 4 weeks of dosing; - to compare the mean trough FEV1, FVC, FEF25-75 observed with CHF 4226 with the one observed with placebo and formoterol after 1 day, 7 days, 14 days and 4 weeks of dosing; - to compare the average FEV1, FVC, FEF25-75 12-24h observed with CHF 4226 with the one observed with placebo and formoterol following the last dosing of test treatments on the evening of day 28; - to characterise FEV1, FVC, FEF25-75 following the last dose at 1, 2, 3 hrs and at 12, 13, 15, 15, 16, 18, 20, 22, 23, 24 time points; - to monitor for safety and tolerability.

Main Objective: To characterise the mean trough 23-24 hrs FEV1 following 4 weeks of treatment (Visit 6/Day 28) of CHF 4226 2µg given q.d. in the evening and to compare it with placebo.

Secondary ID(s)

2006-005689-38-HU

CCD-0604-PR-0018

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 01/01/2017
• Date Completed: 18/07/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-005689-38/results