Effect of Tiotropium on Airway Diameter in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Trial to investigate the acute and chronic effect of tiotropium therapy on airway diameter in COPD patients as measured by inspiratory capacity (IC).

Official Title
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The Effects of Tiotropium Therapy on Airway Diameter in Patients With COPD (a Randomized, Double-blind, Placebo-controlled, Parallel-group Study)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium inhalation powder capsules
* Drug: Placebo inhalation powder capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have a diagnosis of chronic obstructive pulmonary disease Male or female patients ≥ 40 years of age but ≤ 75 years old Patients must have a smoking history of more than ten pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year Patients must be able to perform all specified procedures and maintain records during the study period as required in the protocol Patients must be able to inhale medication from the HandiHaler® All patients must sign a Patient Informed Consent Form prior to participation in the trial i.e., prior to pre-study washout of their usual pulmonary medications Patients must be willing to attend an outpatient clinic on a regular basis Patients must be able to walk 164 feet (50 meters) during the Six Minute Walk Test Exclusion Criteria: Patients with significant diseases other than COPD will be excluded. A significant 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 which may influence the results of the study or the patient's ability to participate in the study Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis test results, if the abnormality defines a disease listed as an exclusion criterion Patients with a serum glutamic-oxaloacetic transaminase (SGOT) ≥1.5 x Upper Limit of Normal Range (ULN), serum glutamic-pyruvic transaminase (SGPT) ≥1.5 x ULN, bilirubin ≥1.5 x ULN or creatinine ≥ 1.5 x ULN regardless of the clinical condition Patients with a recent history (i.e., one year or less) of myocardial infarction Patients with a recent history (i.e., three years or less) of heart failure, pulmonary edema or patients with any cardiac arrhythmia (with or without symptoms) Patients with regular use of daytime oxygen therapy Patients with known active tuberculosis Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed 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 or a thoracotomy for other reason should be evaluated as per exclusion criterion no. 1 Patients with upper respiratory tract infection in the past six weeks prior to the Screening Visit or during the baseline period Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction Patients with known narrow-angle glaucoma Patients who are being treated with cromolyn sodium or nedocromil sodium Patients who are being treated with antihistamines (H1 receptor antagonists) or antileukotrienes and are not able to stop these medications 1 month before visit 1 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 Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600/mm3 Patients with history of (past five years or less) and/or active alcohol or drug abuse Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Period (Visit 1) Patients who have participated in any pulmonary rehabilitation program for COPD within 6 weeks prior to Visit 1 or throughout the study Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea such as arthritis in the leg, angina or claudication

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium<br>Tiotropium inhalation powder capsules 18 mcg, one capsule once daily for 28 days | Drug: Tiotropium inhalation powder capsules<br> <br> |
| Placebo Comparator: Placebo<br>Placebo inhalation powder capsules, one capsule once daily for 28 days | Drug: Placebo inhalation powder capsules<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from time 0 to 3 hours (AUC0-3) of resting inspiratory capacity (IC) |  | Day 28 | 
| Trough resting IC |  | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 (Forced expiratory volume in one second) |  | Day 1, 14 and 28 | 
| FVC (forced vital capacity) |  | Day 1, 14 and 28 | 
| FEF25%-75% (Forced Expiratory Flow, mid expiratory phase) |  | Day 1, 14 and 28 | 
| FEF50% (Forced Expiratory Flow, at 50% of FVC) |  | Day 1, 14 and 28 | 
| FEF75% (Forced Expiratory Flow, at 75% of FVC) |  | Day 1, 14, 28 | 
| SVC (Slow vital capacity) |  | Day 1, 14, 28 | 
| Respiratory System Transfer Impedance (Respiratory Resistance) |  | Day 1, 14 and 28 | 
| Airway Resistance (Raw) |  | Day 1, 14 and 28 | 
| Thoracic Gas Volume (TGV) |  | Day 1, 14 and 28 | 
| Specific Airway Conductance (SGaw) |  | Day 1, 14 and 28 | 
| Physician's Global Evaluation |  | Day 1 and 28 | 
| Oxygen Saturation (SaO2) prior to six minute walk test |  | Day 1 and 28 | 
| Oxygen Saturation (SaO2) post six minute walk test |  | Day 1 and 28 | 
| IC prior to six minute walk test |  | Day 1 and 28 | 
| IC post six minute walk test |  | Day 1 and 28 | 
| Chronic Respiratory Questionnaire (CRQ) |  | Day 1 and 28 | 
| Baseline Dyspnea Index (BDI) |  | Day 1 | 
| Transition Dyspnea Index (TDI) |  | Day 28 | 
| Change from baseline in seated blood pressure |  | Baseline, Day 1, 14 and 28 | 
| Change from baseline in pulse rate |  | Baseline, Day 1, 14 and 28 | 
| Occurrence of Adverse Events |  | until day 35 |