Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
Study to assess the safety of two-week administration of 80 and 160 mcg of ipratropium bromide as delivered by the RESPIMAT® device and as determined by 24 hours ambulatory ECG monitoring in COPD patients. To assess the overall safety of the two doses of ipratropium bromide as delivered by the RESPIMAT® device when administered over a two-week period.
Interventions
DRUGIpratropium Bromide low dose
DRUGPlacebo
DRUGIpratropium Bromide high dose
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
All patients must have a diagnosis of COPD and must meet the following spirometric criteria: * Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 \<=65% of predicted normal and FEV1 \<=70% of forced vital capacity (FVC). Predicted normal value will be calculated according to Morris * Males: FEV1 = 0.093 (Height in inches)-0.032 (age)-1.343 * Females: FEV1 = 0.085 (Height. in inches)-0.025(age)-1.692 * Male or female patients 40 years of age or older * Patients must have a smoking history of more than 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of 20 cigarettes per day for a year * Patients must be able to perform pulmonary function tests (PFTs) and maintain records during the study period as required in the protocol * Patients must be able to be trained in the proper use of an inhalation aerosol and the RESPIMAT™ device * Patients must have a baseline electrocardiogram (ECG) with no clinical relevant arrhythmias or conduction system disease (e.g. right or left bundle branch block, second degree AV block or higher) * Patients must have an oxygen saturation of \>=90% for \>=92% of the recording time on overnight oximetry * All patients must sign an Informed Consent Form prior to participation in the trial (i.e., at least 24 hours (h) prior to the screening visit (Visit 1))
Exclusion criteria
* Patients with clinically relevant diseases other than COPD will be excluded. A clinically relevant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease with may influence the results of the study or patient's ability to participate in the study * Patients with a recent history (i.e. one year or less) of myocardial infarction * Patients with a recent history (i.e. one year or less) of heart failure or patients with any past history or active cardiac arrhythmia requiring drug therapy * Patients who have a pacemaker * Patients with clinically relevant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defines a disease listed as an exclusion criterion the patient is excluded * All patients with serum glutamic oxaloacetic transaminase / Aspartate aminotransferase (SGOT/AST) \>80 IU/L, serum glutamic pyruvic transaminase / Alanine transaminase (SGPT/ALT) \>80 IU/L, bilirubin \>2.0 mg/dl, or creatinine \>2.0 mg/dl will be excluded regardless of the clinical condition. Repeat laboratory evaluation will be not be conducted in these subjects * Patients who have a blood eosinophil count \>=600/mm3. A Repeat eosinophil count will be not be conducted in these patients * Patients with a history of cancer, other than treated basal cell carcinoma, within the last 5 years * Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis * Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reason should be evaluated per exclusion criterion No. 1 * Patients with a history of asthma, allergic rhinitis or atopy * Patients with a history of and/or active alcohol or drug abuse * Patients with known active tuberculosis * Patients with an upper respiratory tract infection or COPD exacerbation in the past 6 weeks prior to the screening visit (Visit 1) or during the baseline period * Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction * Patients with known narrow-angle glaucoma * Patients with current significant psychiatric disorders * Patients with regular use of daytime oxygen therapy * Patients who are being treated with cromolyn sodium or nedocromil sodium * Patients who are being treated with antihistamines * Patients using oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day * Patients who are being treated with beta-blocker medication * Patients who have had changes in their therapeutic plan within the last six weeks prior to the screening visit (visit 1) * Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (e.g., oral contraceptive, intrauterine devices, diaphragm or Norplant®) * Patients with known hypersensitivity to ant cholinergic drugs or any other components of the ATROVENT® RESPIMAT™ solution including bacteriostatic agent benzalkonium chlorid (BAC) and edetic acid (EDTA) * Patients who have taken an investigational drug within 1 month or 6 half-lives (whichever is longer) prior to the screening visit (visit1) * Previous participation in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of clinical significant findings in 24-hour ambulatory ECG monitoring | Pre-treatment, on Day 7 and 13 |
| Number of patients with adverse events | Up to 15 days after first drug administration |
| Number of patients with clinical significant findings in ECG | Up to 15 days after first drug administration |
| Number of patients with clinical significant findings in vital signs | Up to 15 days after first drug administration |
| Number of patients with clinical significant findings in laboratory tests | Up to day 15 after drug administration |
| Number of patients with paradoxical bronchospasm | Up to 15 days after first drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Cmin(0h) (minimum plasma concentration before inhalation) | Day 14 |
| Cmin(6h) (minimum plasma concentration at 6 hours after inhalation) | Day 14 |
| FEV1 (forced expiratory volume in the first second) AUC0-4 (Area under the curve from 0 to 4 hours) | Pre-treatment, up to 4 h after drug administration on Day 1 and 14 |
| Ae(0-6h) (urine excretion between 0 to 6 h) | Day 14 |
| Ae(0-2h) (urine excretion between 0 to 2 h) | Day 14 |
| Peak FEV1 | On Day 1 and 14 |
| Onset of therapeutic FEV1 response | On Day 1 and 14 |
| Time to peak FEV1 response | On Day 1 and 14 |
| AUC(0-6h) (Area under the plasma concentration-time curve from 0 to 6 h) | Day 14 |
| Cmax (maximum plasma concentration) | Day 14 |
Outcome results
None listed