To investigate the effects of beclomethasone plus formoterol (in a single inhaler) versus single agents formoterol and beclomethasone dipropionate pMDI with HFA-134a propellant and placebo on the airway responses to allergen challenge. The primary…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To demonstrate that CHF 1535 as single administration is superior to single
components and to placebo in terms of late asthmatic response (LAR), when given
after inhaled allergen challenge.
Secondary outcome
To assess the effects of the study drugs on early asthmatic response (EAR),
airway hyperresponsiveness, induced sputum differential cell counts and
inflammatory mediators in supernatant, fractional exhaled nitric oxide (FeNO)
values and changes in VOCs behaviour.
Background summary
The management of asthma is currently focused on achieving optimal asthma
control and reducing exacerbations. In mild asthma this can be achieved with
ICS monotherapy, in moderate to severe persistent asthma with the addition of a
(LABA: salmeterol or formoterol) to the ICS. Combination therapies are more
convenient to use, control asthma at lower doses of ICS and ensure that the ICS
are not discontinued when LABA is added. A new pharmacological approach is
called SMART (Symbicort Maintenance and Reliever Therapy). The patient is
taking a fixed dayly dose of the combination therapy for asthma control and an
additional dose in response to symptoms. The most striking explanation at the
basis of the SMART approach is that taking additional doses of the combination
at the first signs of asthma worsening, it could be possible to extinguish
airway inflammation at an early stage and prevent its evolution toward a more
relevant inflammatory process into the airways leading to the clinical
manifestations of exacerbation. This rationale is supported by recent evidences
that asthma exacerbations are not rapid events, but evolve slowly over several
days.
Study objective
To investigate the effects of beclomethasone plus formoterol (in a single
inhaler) versus single agents formoterol and beclomethasone dipropionate pMDI
with HFA-134a propellant and placebo on the airway responses to allergen
challenge. The primary objective will be to demonstrate that CHF 1535 as single
administration is superior to single components and to placebo in terms of late
asthmatic response (LAR), when given after inhaled allergen challenge. The
secondary objectives will be the assessment of study drugs on early asthmatic
response (EAR), airway hyperresponsiveness, induced sputum differential cell
counts, inflammatory mediators in supernatant, fractional exhaled nitric oxide
(FeNO) values and volatile organic compounds detected with electronic nose.
Study design
Single centre, double blind, single dose, randomized, 4-period cross-over,
placebo-controlled clinical study
Intervention
1. Foster (extrafine beclomethasone dipropionate 100 µg + formoterol fumarate
6 µg)
2. extrafine beclomethasone dipropionate 100 µg
3. formoterol fumarate 6 µg
4. placebo
Each patients recieves a single dose of each intervention (cross-over). The
treatment is given in four randomized, cross-over treatment periods, each
composed of 3 consecutive days separated by 4 to 6 weeks of washout.
Study burden and risks
with each patient the following measurements will be performed:
14 x spirometry
1 x skin prick test
9 x methacholine/histamin challenge (PC20)
1 x ECG
11 x physical examination
1 x medical history
11 x vital signs
5 x allergenchallenge
16 x FeNO measurement
9 x electronic nose
8 x sputum induction
1 x blood sample
The patient will spend a total of 80 hours at the department.
The possible risks are:
- immediately after the inhalation of the allergen patients can have a
reduction of the lung function, which will then carefully be monitored before
and after the study drug administration and the symptoms will be adequately
treated with adequate rescue medications and facilities.
The inhalation of formoterol may sometimes cause side effects of a brief
duration such as tremors of the hands (usually transitory, related to the dose
and disappearing with the treatment continuation), cephalgias, palpitations,
tachycardia, skin allergy and muscular cramps.
The use of an inhaled corticosteroid such as beclomethasone might primarily
induce local effects such as pharyngeal discomfort, dysphonia, voice hoarseness
indeed even a secondary event of a fungal infection of the throat. All these
adverse effects can be prevented by a rinsing of the mouth with water after
inhalation.
Albinusdreef 2
2333 ZA Leiden
NL
Albinusdreef 2
2333 ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent
- Male and female outpatients, aged * 18 years and * 55 years
- Clinical diagnosis of atopic controlled asthma for at least 6 months, according to Global Strategy for Asthma Management and Prevention (GINA) revised version 2006 Guidelines, without severe exacerbation in the previous 6 months before study entry
- Patients only taking short-acting *2-agonists on an as needed basis
- A provocative concentration of methacoline chloride or histamine causing a 20% fall in FEV1 (PC20) < 8 mg/ml
- A positive skin prick test (SPT) for house dust mite
- A documented EAR (* 20% fall in FEV1 from baseline, 0-3 h post allergen) and a LAR (* 15% fall in FEV1 from baseline, 3-8 h post-allergen) following inhaled allergen extract
- A co-operative attitude and ability to correctly use the device
Exclusion criteria
- Current smokers or recent (less than one year) ex-smokers
- Evidence of severe asthma exacerbation in the previous 6 months
- Clinically significant history of upper/lower respiratory tract infection within 4 weeks from the start of the study
- Clinically significant or unstable concurrent disease : e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; significant other pulmonary disease; cardiovascular disease; gastrointestinal disease; neurological disease; haematological disease, autoimmune disorders, laboratory and electrocardiographic abnormalities that may interfere with patient*s safety, compliance, or study evaluations, according to the investigator*s opinion
- Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature). A pregnancy test in urine is to be carried out in women of a fertile age at screening
- Patients treated with long-acting *2-agonists, anticholinergics and antihistamines and with topicalcorticosteroids and leukotriene antagonists during the previous 4 weeks
- Patients treated with beta-blockers in the week preceding the screening visit
- Patients who received systemic steroids in the previous 2 month
- Significant alcohol consumption or drug abuse
- Patients with allergy, sensitivity or intolerance to sympathomimetic drugs or corticosteroids or to any of the excipients contained in the study drugs
- Inability to perform spirometry of acceptable quality (according to ERS guidelines)or any other acute or chronic condition that put the patient at risk or may alter the interpretation of the test.
- Patients who received any investigational new drug or participated in clinical study within the previous 8 weeks before study entry
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-002844-40-NL |
| CCMO | NL23421.058.08 |