A clinical trial to assess the most efficacious dose of bronchodilator, Glycopyrrolate, to add to the existing treatment (Foster, Beclomethasone + Formoterol) for the development of a new triple therapy in a single aerosol for the treatment of patients suffering from severe COPD.
- Conditions
- Chronic Obstructive Pumlonary DiseaseMedDRA version: 14.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2011-003588-31-IT
- Lead Sponsor
- CHIESI
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 180
1. Male and female adults (40 = age = 80 years) with written informed
consent obtained prior to any study-related procedure.
2. Outpatients with a diagnosis of COPD (according to GOLD guidelines)
with:
A smoking history of at least 10 pack years (pack-years = ((number of
cigarettes per day x number of years)/20). Current and ex-smokers are
eligible.
(Smoking cessation therapy must be completed within 3 months prior to
screening visit and smoking status shall not change after screening and
during the study period)
- A Post-bronchodilator 30%=FEV1<60% of the predicted normal value
- A Post-bronchodilator FEV1/FVC < 0.7
- An increase from baseline of FEV1 value 30 min after 80µg ipratropium
of at least 60mL
3. Patients treated with double therapy with inhaled
corticosteroids/long-acting ß-agonist combination or with triple therapy
with inhaled corticosteroids/long-acting ß-agonist combination and
long-acting anticholinergic (tiotropium) if taken for not more than one month at stable regimen before screening.
4. A cooperative attitude and ability to be trained to use correctly the
pMDI inhalers.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 108
1.Pregnant or lactating women.
In case of childbearing potential, patients and/or their partner must be willing to use an approved method of contraception unless they meet the post-menopausal definition (amenorrhea>12 Mo or >6 Mo with FSH >40 mIU/ml). Methods of contraception may include one or more of the following ones: Surgical sterilization, hormonal contraception, doublebarrier methods and periodic abstinence. Reliable contraception should be maintained throughout the study.
2.Diagnosis of asthma or history of allergic rhinitis or atopy.
3.Participation in another clinical trial where investigation drug was received less than 8 weeks prior to first intake of the study medication.
4.Hospitalisation for COPD or pneumonia within 3 month prior to screening
5.Patients experiencing a COPD exacerbation requiring use of systemic steroids and/or antibiotics in the 4 weeks prior to screening and during the run-in period.
6.Patients treated with oral/parenteral ß2-agonists or nebulised bronchodilators or PDE inhibitors in the 4 weeks prior to screening and during the run-in period.
7.Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening and during the run-in period.
8.Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
9.Known respiratory disorders other than COPD including but not limited to alpha-1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and
interstitial lung disease.
10.Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic.
11.History of hypersensitivity to M3 Antagonists, ß2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial.
12.History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit
13.An abnormal and clinically significant 12-lead ECG that results in active medical problem.
14.Electrocardiogram (ECG) (12 lead) with QTcF >450 ms for males or QTcF > 470 ms for females.
15.Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the feasibility of the results of the study according to investigator's judgement.
16.Patients with serum potassium levels < 3.5 mEq/L (or 3.5 mmol/L).
17.Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; cardiovascular disease
(e.g. uncontrolled coronary artery disease, uncontrolled hypertension); uncontrolled gastrointestinal disease (e.g. active peptic ulcer); neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the feasibility of the
results of the study according to investigator's judgment.
18.Evidence of heart failure (NYHA class IV).
19.Changes in dose, schedule, formulation or product of oral xanthine derivatives (eg theophylline) in the three months prior to screening visit.
20.Change in dose, schedule, formulation or product of ß-blockers in the month prior to screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of a free combination of glycopyrrolate at 3 dose<br>levels with fixed combination beclomethasone dipropionate plus<br>formoterol (Foster) in a metered dose inhaler by comparison with<br>Foster in terms of FEV1 AUC0-12h normalized by time on Day 7.;Secondary Objective: To evaluate the effect of the free combination glycopyrrolate + Foster on<br>other lung function parameters and on clinical outcome measures. To<br>assess the safety and the tolerability of the study treatments.;Primary end point(s): FEV1 AUC0-12h normalized by time on Day 7;Timepoint(s) of evaluation of this end point: Day 7
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Day 1, 7 and 8;Secondary end point(s): Efficacy variables:<br>•Trough FEV1, FVC and IC at 12 h on Day 1 and Day 7 (mean of the two<br>measurements at 12h and 12.5h post-dose)<br>•Trough FEV1, FVC and IC at 24h (mean of the two measurements at<br>23.5h and 24h post-dose) on Day 7 (i.e. on the morning of Day 8)<br>•FEV1 AUC0-12h normalised by time on Day 1<br>•FEV1 AUC0-24h and AUC12-24h normalised by time on Day 7<br>•Peak FEV1, FVC and IC on Day 1 and Day 7<br>•FEV1, FVC and IC at each time point on Day 1 and Day 7<br>•Transition Dyspnoea Index (TDI) score on Day 8<br>•Average use of rescue medication (number of puffs/day) during the<br>treatment period<br>•Percentage of rescue use-free days during the treatment period<br>Safety variables:<br>•Adverse events and adverse drug reactions<br>•Vital signs (systolic and diastolic blood pressure, heart rate)<br>•Standard haematology and blood chemistry<br>•12-lead ECG