Primary objective:To demonstrate the higher efficacy of small particles Foster® 100/6 (two puffs b.i.d.) versus large particles Symbicort® 200/6 (two inhalations b.i.d.), in terms of residual volume reduction in patients with chronic obstructive…
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary efficacy variables
Change from baseline to end of treatment in post-dose residual volume.
Secondary outcome
Secondary efficacy variables
- Changes from baseline in FEV1, FVC, FEV1/FVC, IVC/FVC, RV, TLC, RV/TLC, FRC,
FRC/TLC, RV/VC, Raw, eff and sGaw, eff.
- Changes from baseline in airways resistance (R5, R20, R5-20) and reactance at
5 Hertz (X5) (in a subset of at least 50% of patients from pre-selected sites);
- Changes from baseline in COPD symptom scores (for each single score and the
total score);
- Change from baseline in percentage of COPD symptom-free days;
- Change from baseline in rescue salbutamol or ipratropium bromide consumption
(puffs per day);
- Change from baseline in percentage of rescue salbutamol or ipratropium
bromide-free days;
- Transition Dyspnoea Index (TDI) score at day 84 (V4);
- Clinical COPD Questionnaire (CCQ);
- Physical activity (by means of pedometer);
- Nasal brushing (mRNA expression);
- Number of patients with COPD exacerbations.
Background summary
Chronic obstructive pulmonary disease (COPD) is an incurable, debilitating and
progressive disease that can be fatal. The recent Global Burden of Disease
Study ranks COPD as the 6th leading cause of mortality and the 12th leading
cause of morbidity world-wide. Furthermore, trends in the use of medical care
resources indicate that the economic cost of COPD continues to rise in direct
relation to the ageing population, the increase in prevalence of disease and
the cost of new and existing medical and public health interventions.
The purpose of the present study is to demonstrate the higher efficacy of small
particles Foster® 100/6 (two puffs b.i.d.) versus large particles Symbicort®
200/6 (two inhalations b.i.d.), in terms of residual volume reduction in
patients with chronic obstructive pulmonary disease. In addition, we will
evaluate the efficacy of the test treatments in terms of reduction of symptoms,
improvements in health status (assessed by specific questionnaires) and in
parameters related to the function of small airways in chronic obstructive
pulmonary disease, and we will assess the safety.
Study objective
Primary objective:
To demonstrate the higher efficacy of small particles Foster® 100/6 (two puffs
b.i.d.) versus large particles Symbicort® 200/6 (two inhalations b.i.d.), in
terms of residual volume reduction in patients with chronic obstructive
pulmonary disease.
Secondary objectives:
To evaluate the efficacy of the test treatments in terms of reduction of
symptoms, improvements in health status (assessed by specific questionnaires)
and in parameters related to the function of small airway function in patients
with Chronic Obstructive Pulmonary Disease, and to assess the safety of study
treatments.
Study design
This is a phase IIIb, multicentre, randomized, double-blind, double-dummy,
2-arm parallel group design preceded by a 4-week run-in period in 144 patients
aged >= 40 years with COPD. The study will compare the efficacy and safety of
Foster® 100/6 (two puffs b.i.d.) versus Symbicort® 200/6 (two inhalations
b.i.d.), over a 12-week treatment period.
The study plan foresees:
-A pre-screening visit (V0, at week -5 before the randomization visit) during
which clinical instructions to determine patients* adaptability to the study
procedures will be performed. This can be done only after the participants have
agreed to participate and have signed the Informed Consent form.
-A screening visit (V1, week -4) in which patients with COPD and lung
hyperinflation will be selected.
-A 4-week run-in period where patients will receive a standardised treatment
with Symbicort® Turbohaler® 200/6 µg, 1 inhalation b.i.d. (daily dose of BUD
400 µg plus FF 12 µg) and have any non-permitted medications withdrawn prior to
entry into test treatment period.
-A randomisation visit (V2, week 0) during which patients will be allocated to
one of the two treatment arms, and subsequent visits taking place at clinics
after 4 weeks (V3) and after 12 weeks (V4) of treatment. After 8 weeks of
treatment, a phone contact to document and treat adverse events occurred since
the last visit, to record any change of concomitant medications being taken by
the patient and to document any consumption of medical resources will be
performed. The end of the trial is defined as the last visit of the last
subject on the trial. After 7-10 days of last study medication intake, a
follow-up phone contact to check the status of any adverse event which was
still unresolved at the last visit will be performed.
Intervention
Treatment A: Foster® (beclomethasone dipropionate100 µg plus formoterol 6 µg),
twice a day 2 puffs Foster®
twice a day 2 inhalations Symbicort ® Turbohaler® placebo
Treatment B: Symbicort® Turbohaler® (budesonide 200 µg plus formoterolfumarate
6 µg)
twice a day 2 puffs Foster® placebo
twice a day 2 inhalations Symbicort ® Turbohaler
Study burden and risks
All drugs may cause side effects. Beclomethasone dipropionate and formoterol
are medicinal products that have been on the market for many years in many
countries. The study medication Foster® is a combination similar to other
combinations (Symbicort®, Seretide®) available on the market; therefore side
effects associated with each of the compounds and similar to those reported for
the other combinations may be expected.
Possible adverse effects are listed below, in order of their frequency of
occurrence.
- Common (affecting less than 1 in 10 people):
Headache, hoarseness, sore throat.
- Uncommon (affecting less than 1 in 100 people):
- Palpitations, unusual fast heart beat and disorders of heart rhythm, some
changes in the electrocardiogram (ECG).
- Flu symptoms, fungal infections (of the mouth and throat), fungal infections
of the vagina, inflammation of the sinuses, rhinitis, inflammation of the ear,
throat irritation, cough and productive cough, asthma attack.
- Nausea, abnormal or impaired sense of taste, burning of the lips, dry mouth,
swallowing difficulties, indigestion, upset stomach, diarrhoea.
- Pain in muscle and muscle cramps, reddening of the face, increased blood flow
to some tissues in the body, excessive sweating, trembling, restlessness,
dizziness.
- Alterations of some constituents of the blood: fall in the number of white
blood cells, increase in the number of blood platelets, a fall in the level of
potassium in the blood, increase in blood sugar level, increase in the blood
level of insulin, free fatty acid and ketones.
- Rare (affecting less than 1 in 1,000 people):
Feeling chest tightness, missed heartbeat (caused by too early contraction of
the ventricles of the heart), increased or decrease in blood pressure,
inflammation of the kidney, swelling of skin and mucous membrane persisting for
several days, nettle rash or hives.
- Very rare (affecting less than 1 in 10,000 people):
Irregular heartbeat, shortness of breath, worsening of asthma, abnormal
behaviour, sleep disorders and hallucinations, a fall in the number of blood
platelets, swelling of the hands and feet.
There is a potential risk of unforeseeable allergic reactions as for any drug.
Hypersensitivity reactions like skin allergies, skin itching, skin rash,
reddening of the skin, swelling of the skin or mucous membranes especially of
the eyes, face, lips and throat may occur.
As with other inhaler treatments there is a risk of worsening shortness of
breath and wheezing immediately after using (paradoxical bronchospasm).
Using high-dose inhaled corticosteroids over a long time can cause in very rare
cases systemic effects: these include problems with how adrenal glands work
(adrenosuppression), decrease in bone mineral density (thinning of the bones),
growth retardation in children and adolescents, increased pressure in eyes
(glaucoma), cataracts.
In case of any health problem related to the study the patient will immediately
receive the adequate treatment.
In case the patient has to use salbutamol or ipratropium bronmide, which will
be provided as a rescue medication during the study, the patient may possibly
experience side effects associated with this drug: the most common are
headache, dizziness, tremor, cough and local irritation. Occasionally, muscle
cramps, tachycardia and palpitations.
The patient may experience minor discomfort from the blood sampling procedures,
and occasionally some bruising or inflammation of the veins used for blood
sampling. These effects normally disappear within a few days.
For female patients, there may be unknown risks to the foetus (unborn child).
If the patient is a female patient of childbearing potential, the patient must
not be pregnant and not intend to become pregnant during the whole study
period. Women of childbearing potential have to use during their study
participation and 30 days after a reliable method of contraception which will
be: surgical sterilization (e.g. bilateral tubal ligation, hysterectomy),
hormonal contraception (oral, implantable, patch, injectable), barrier methods
[condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/cream/suppository)] or continuous abstinence (e.g. nuns). At visits 1
and visit 4, a blood pregnancy test is to be carried out if the patient a woman
of a fertile age. As well breast feeding women are not allowed to participate
in this study, because the study drug may enter the child*s body through the
breast milk and cause harm. If a patient becomes pregnant in spite of
precautions during the study period, the patient need to contact the study
doctor instantly, who will withdraw the patient immediately from the study.
Male patients must immediately inform the study doctor in case your partner
becomes pregnant during your participation in the study
The patient will not be allowed to take some drugs: your study doctor will
inform the patient about the medications not permitted during the study. In
case of change of concomitant medications during the study, the patient must
inform the study doctor beforehand.
The patient may not have participated in another trial with the study drugs
(investigational drugs) in the 2 months prior to this study and must not
participate in any other study for the time this one is ongoing.
The information obtained from this study may help us to propose in the future a
new effective combination drug to the patients with COPD which is expected to
have a positive effect on patient compliance (i.e., the patient adheres to the
doctor*s instructions for treatment intake) to treatment and to improve the
patient condition.
No matter which group the patient is assigned to, the patient will receive an
active treatment for his disease which is expected to improve your lung
functions. Moreover, the patient's disease and overall condition will be
carefully and closely evaluated by the study doctor; this will help the doctor
to assign you a more suitable drug therapy when the study is over (either by
changing the dose of the drugs the patient was taking previously or by adding
additional drug(s), etc.).
Via Palermo 26/A
43122 PARMA
IT
Via Palermo 26/A
43122 PARMA
IT
Listed location countries
Age
Inclusion criteria
Inclusion criteria
1. Male or female patients aged >= 40 years, who have signed an Informed Consent form prior to initiation of any study-related procedure or when applicable written informed consent obtained by legal representative.
2. Outpatients with a clinical diagnosis of severe to very severe COPD and including:
a) Smoking history of at least 10 pack years defined as [(number of cigarettes smoked per day) * (number of years of smoking)] / 20, both current and ex-smokers are eligible.
b) Regular use of bronchodilators (e.g. β2-agonist, anticholinergics) in the 2 months before visit 1.
c) Post-bronchodilator FEV1 < 50% of the predicted normal value at visit 1.
d) Post-bronchodilator FEV1/FVC < 0.7 at visit 1.
f) Plethysmographic Functional Residual Capacity (FRC) > 120% of the predicted normal value (at visit 1 and visit 2).
g) A Baseline Dyspnoea Index (BDI) focal score <=*10 (at visit 1 and at visit 2).
3. A cooperative attitude and ability to be trained to the proper use of pMDI and DPI (Turbohaler®, inspiratory flow-driven, multidose powder inhaler) inhalers.
Exclusion criteria
Exclusion criteria
1. Diagnosis of asthma or other clinically or functionally relevant respiratory disorders (other than COPD) which may interfere with data interpretation according to the investigator*s opinion.
2. Pregnant or lactating women. Females of childbearing potential without an efficient contraception UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or are using one or more of the following acceptable methods of contraception:
a) surgical sterilization (e.g. bilateral tubal ligation, hysterectomy);
b) hormonal contraception (implantable, patch, oral, injectable);
c) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.
3. Clinically unstable concurrent disease: e.g. hyperthyroidism, diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; cardiovascular disease (e.g. coronary artery disease, hypertension, heart failure); gastrointestinal disease (e.g. active peptic ulcer); neurological disease; haematological disease; autoimmune disorders, or other which may impact the evaluation of the results of the study according to investigator*s judgement.
4. Patient with narrow-angle glaucoma.
5. Clinically significant laboratory and ECG abnormalities indicating a significant or unstable concomitant disease which may impact the evaluation of the results of the study and the safety of the patient according to investigator*s judgement.
6. Patients with COPD exacerbation and/or symptomatic infection of the airways requiring antibiotic therapy (at least 5 days) in the 2 months prior to screening and during the study period. COPD exacerbation will be defined according to the following: *A sustained worsening of the patient*s condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD that includes prescriptions of systemic corticosteroids (at least 3 days) and/or antibiotics (at least 5 days), or need for a visit to an emergency department or hospitalization*.
7. Patients requiring long term (> 12 hours daily) oxygen therapy for chronic hypoxemia.
8. Patients treated with depot corticosteroids in the 2 months preceding the visit 1 and during the run-in period.
9. Patients with known allergy, sensitivity or intolerance to sympathomimetic drugs or inhaled corticosteroids or to any of the excipients contained in the study drugs.
10. Patients who have evidence of alcohol or drug abuse, not compliant with the study protocol or not compliant with the study treatments according to investigator*s judgement.
11. Major surgery in the previous 3 months and during the trial which may affect patient*s compliance in study procedures (e.g. plethysmography).
12. Participation in another clinical trial with an investigational drug in the 2 months preceding visit 1.
13. Patients requiring chronic mechanical ventilation for COPD.
Design
Recruitment
Medical products/devices used
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 | EUCTR2010-022895-30-NL |
| CCMO | NL36468.042.11 |