Phase III placebo controlled crossover trial to better characterise the acute effect of LAS 34273 on bronchodilation action in severe COPD patients. MedDRA version: 8.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease
Conditions
Interventions
Product Name: Aclidinium Bromide
Product Code: LAS 34273
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Aclidinium bromide
CAS Number: 320345-99-1
Current Sponsor code: LAS-34273
Concentr
Sponsors
Laboratorios Almirall, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and non-pregnant, non-lactating females aged = 40. Women of childbearing potential are allowed to enter the trial ONLY if they use one medically approved (i.e., mechanical or pharmacological) contraceptive measures. A female is considered to be of childbearing potential unless she has had an hysterectomy, is at least one year post-menopausal or has undergone tubal ligation. All women of childbearing potential must have a negative pregnancy test at screening visit. 2. Patients with a clinical diagnosis of COPD, according to the GOLD guidelines: (http://www.goldcopd.com) and stable airway obstruction. 3. Patients with a post-salbutamol FEV1 equal or greater than 30% of the predicted value and less than 60% of the predicted value (i.e., 30% = 100xobserved post-salbutamol FEV1/ predicted FEV1 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History or current diagnosis of asthma, allergic rhinitis or atopy 2. Eosinophil count > 600 cells/mm3. 3. A respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks prior to screening visit. Patients who develop a respiratory tract infection or exacerbation during the screening period will be discontinued from the trial prior to randomisation. 4. Patients who have been hospitalised for an acute COPD exacerbation in the 3 months prior to screening visit. 5. Use of long-term oxygen therapy (= 15 hours/day). 6. Clinically significant respiratory conditions defined as: • Known active tuberculosis. • History of interstitial lung or pulmonary thromboembolic disease. • Pulmonary resection during the past 12 months. • History of life-threatening COPD. • History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc). • Patients who in the investigator’s opinion may need pulmonary rehabilitation or a thoracotomy during the trial. 7. Clinically significant cardiovascular conditions defined as: • Myocardial infarction during the last 6 months. • Unstable arrhythmia which has required changes in the pharmacological therapy or other intervention during the last 12 months, or newly diagnosed arrhythmia within the previous 3 months. • Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association. 8. Patients in whom the use of anticholinergic drugs is contraindicated: those with a known symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma. 9. Patients with any other serious or uncontrolled physical or mental dysfunction at the discretion of the investigator which could place the patient at higher risk derived from his/her participation into the study, could confound the results of the trial or is likely to prevent the patient from complying with the requirements of the trial or completing the trial period. 10. QTc [calculated according to Bazett’s formulae (QTc=QT/RR1/2) above 470 milliseconds in the ECG performed at screening visit. 11. Patients who do not demonstrate to perform reproducible spirometry attempts at screening visit. 12. History of untoward reactions to inhaled anticholinergics, sympathomimetic amines or inhaled medication or any component thereof (including report of paradoxical bronchospasm). 13. Patients unable to properly use a dry powder or pMDI inhaler device or to perform spirometry. 14. Clinically relevant abnormalities in the results of laboratory, ECG parameters, other than QTc, or physical examination at the screening evaluation if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD. 15. Patients who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication. 16. Patients with a history of drug and/or alcohol abuse that may prevent compliance with trial activities. 17. Patients who have participated in other studies involving LAS 34273. 18. Treatment with any Investigational Medicinal Product (IMP) within 1 month prior to screening visit or the equivalent time to 6 ha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the rate of onset of bronchodilator action of inhaled LAS 34273 compared to placebo.;Secondary Objective: To assess the rate of onset of action of inhaled LAS 34273 compared to tiotropium 18 µg and to placebo. ;Primary end point(s): Primary variable: - Percentage of patients achieving a FEV1 increase from baseline equal to or greater than 10% at 30 min. Main secondary variables: - Normalised FEV1 AUC0-3 h. - Change from baseline in FEV1 at 30 min. Additional variables: - Percentage of patients achieving a FEV1 increase from baseline equal to or greater than 10% at other timepoints. - Percentage of patients achieving a FEV1 increase from baseline equal to or greater than 12% and 15% at all timepoints. - Change from baseline in FEV1 at other timepoints. - Change from baseline in FVC, FEF25-75% and IC at all timepoints. - Maximal changes from baseline in FEV1, FVC, FEF25-75% and IC. - Time to maximal change in FEV1, FVC, FEF25-75% and IC. - Normalised AUC0-30min and AUC0-1 h of FEV1, FVC and FEF25-75%, normalised AUC0-3 h of IC. - Change from baseline in perception of dyspnoea assessed with a visual analogue scale (VAS) at all timepoints. Safety Assessments - All adverse events. - All serious adverse events. - Physical examination (including blood pressure). - Laboratory assessments (standard haematology, biochemistry and urinalysis). - 12-lead ECG parameters. | — |
Countries
Germany, Netherlands, United Kingdom
Outcome results
None listed