Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This pharmacodynamic and pharmacokinetic dose-ranging study aims to determine the optimal dose of tiotropium inhaled as a solution from a Respimat device once a day for three weeks in patients with COPD.
Interventions
DRUGTiotropium 0.625 mcg/puff
DRUGTiotropium 1.25 mcg/puff
DRUGTiotropium 2.5 mcg/puff
DRUGTiotropium 5 mcg/puff
DRUGPlacebo solution
DRUGTiotropium-18 lactose powder
DRUGTiotropium 10 mcg/puff
DEVICERespimat
DEVICEHandihaler
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age: ≥ 40 years; 2. Diagnosis of COPD and met the following criteria: 1. Relatively stable, moderate to severe airway obstruction, 2. Baseline 30% ≤ FEV1 ≤ 65% of predicted normal value, predicted normal values are based on the guidelines for standardized lung function testing of the European Community for Coal and Steel (ECCS) , 3. Baseline FEV1/ forced expiratory vital capacity (FEVC) ≤ 70%; 3. Smoking history ≥ 10 pack-years (p.y.). A p.y. is defined as the equivalent of smoking one pack of cigarettes per day for one year; 4. Male of female; 5. Ability to be trained in the proper use of Respimat and Handihaler; 6. Ability to be trained in the performance of technically satisfactory pulmonary function tests; 7. Ability to provide written informed consent 8. Patient affiliated to the Social Security System
Exclusion criteria
1. History of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³ 2. Changes in the therapeutic (pulmonary) plan within the last six weeks prior to the Screening Visit; 3. Treatment by cromolyn/nedocromil sodium; 4. Treatment by antihistamines (H1 receptor antagonists); 5. A lower respiratory tract infection or any exacerbation in the past six weeks prior to the Screening Visit; 6. Regular use of daytime oxygen therapy; 7. Treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose \> 10 mg prednisone equivalent; 8. History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis 9. Patients who have undergone thoracotomy with pulmonary resection; 10. History of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. A clinically significant disease was defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study. 11. Patients with a recent (≤ one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy; 12. Tuberculosis with indication for treatment; 13. History of cancer within the last five years. Patients with treated basal cell carcinoma were allowed: 14. Current psychiatric disorders; 15. Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction; 16. Patients with any history of glaucoma or increased intra-ocular pressure; 17. Patients with clinically significant abnormal baseline haematology or blood chemistry, if the abnormality defines a disease listed as an exclusion criterion; 18. Patients with 1. glutamyl-oxalo-acetic transaminase/glutamyl-pyruvic transaminase (SGOT/SGPT): \> 200% of the upper limit of the normal range (ULN, ) 2. bilirubin: \> 150% of the ULN, 3. creatinine: \> 125% of the ULN; 19. Intolerance to aerosolised anticholinergic containing products, and/or hypersensitivity to benzalkonium chloride, to lactose or any other components of the inhalation capsule delivery system; 20. Beta-blocker medication; 21. Concomitant or recent (within the last month) use of investigational drugs; 22. History of drug abuse and/or alcoholism; 23. Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception ( urinary pregnancy test at screening); 24. Previous participation in this study (i.e. having been allocated a randomised treatment number); 25. Patients deprived of their freedom by a judicial or administrative decision; 26. Minors, adults under guardianship; 27. Persons in medical or social establishments; 28. Patients in emergency situations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forced expiratory volume in one second (FEV1) with emphasis on the last two hours of the 24-hour dosing interval (trough FEV1) | last two hours of the 24-hour dosing interval |
Secondary
| Measure | Time frame |
|---|---|
| Forced Vital Capacity (FVC) | during first four hours post dose |
| Pharmacokinetic evaluation: 2-hours urine sampling pre- and post-dose (10 patients per group) | before and after last drug administration at day7,14 and 21. |
| Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication | 3 weeks treatment period |
| Forced expiratory volume in one second (FEV1) | during the first four hours post dose |
| Changes in ECG, physical examination, haematology and biochemistry recorded before and after the trial | Screening, 24 to 28 days after treatment |
| Occurrence of adverse events | up to 28 days |
| Changes in ECG, pulse rate (PR) and blood pressure (BP) from the pre-dose values recorded on test day | Day 0, day 7, day 14, day 21 |
Outcome results
None listed