Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)

Overview

The objective of this study is to compare the long-term (six month) bronchodilator efficacy and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo inpatients with COPD.

Full Title of Study: “A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 2000

Interventions

  • Drug: Tiotropium inhalation powder capsules
  • Drug: Salmeterol inhalation aerosol
  • Drug: Placebo inhalation aerosol
  • Drug: Placebo inhalation powder capsules

Arms, Groups and Cohorts

  • Experimental: Tiotropium
  • Active Comparator: Salmeterol
  • Placebo Comparator: Placebo

Clinical Trial Outcome Measures

Primary Measures

  • Trough forced expiratory volume in one second (FEV1) response
    • Time Frame: 6 months
  • Transition Dyspnoea Index (TDI) focal score
    • Time Frame: 6 months

Secondary Measures

  • Average FEV1 response
    • Time Frame: 30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
  • Peak FEV1 response
    • Time Frame: 30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
  • Trough FVC (forced vital capacity) response
    • Time Frame: 30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
  • Average FVC (forced vital capacity) response
    • Time Frame: 30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
  • Peak FVC (forced vital capacity) response
    • Time Frame: 30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
  • Individual FEV1 measurement
    • Time Frame: Day 1, weeks 2, 8, 16, 24
  • Individual FVC measurement
    • Time Frame: Day 1, weeks 2, 8, 16, 24
  • Patient peak expiratory flow rates (PEFR) twice daily
    • Time Frame: 27 weeks
  • Physician’s global evaluation on an 8-point-scale
    • Time Frame: 27 weeks
  • COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest)
    • Time Frame: 27 weeks
  • Amount of salbutamol therapy used during the treatment period
    • Time Frame: 27 weeks
  • Number and length of exacerbations of COPD
    • Time Frame: 27 weeks
  • Number and length of hospitalizations for respiratory disease
    • Time Frame: 27 weeks
  • Changes from baseline in St. George’s Hospital Respiratory Questionnaire (SGRQ)
    • Time Frame: Day 1, week 8, 16, 24 and 27
  • Changes from baseline in Mahler Dyspnoea Index (Baseline Dyspnoea Index /Transitional Dyspnoea Index (BDI/TDI))
    • Time Frame: Baseline, week 8, 16, 24, 27
  • Health resource utilisation
    • Time Frame: 27 weeks
  • Patient preference measures
    • Time Frame: Day 1 and week 24
    • patient satisfaction questionnaire score
  • Changes from baseline in Shuttle walking tests (SWT) and Borg dyspnea score
    • Time Frame: Day 1, week 8, 16, 24, 27
  • Occurrence of Adverse Events
    • Time Frame: 27 weeks
  • Changes from baseline in pulse rate and blood pressure in conjunction with spirometry
    • Time Frame: baseline, Day 1, week 2, 8, 16 and 24
  • Changes from baseline in physical examination and ECG
    • Time Frame: baseline and week 24
  • Changes from baseline in laboratory tests
    • Time Frame: baseline and week 24

Participating in This Clinical Trial

Inclusion Criteria

  • Age ≥ 40 years. – A diagnosis of relatively stable, moderate to severe COPD with: – Screening FEV1 ≤ 60% of predicted normal value (calculated according to European Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC ≤ 70% – Smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent) – Ability to be trained in the proper use of the HandiHaler® device and Metered Dose Inhaler (MDI). – Ability to perform all study related tests including the Shuttle Walking Test, acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR) measurements, and maintenance of diary card records. – Ability to give written informed consent in accordance with Good Clinical Practice and local regulations. Exclusion Criteria:
  • Clinically significant diseases other than COPD. – Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded. – All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition. – A recent history (i.e., one year or less) of myocardial infarction. – Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years. – Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day. – Known active tuberculosis. – History of cancer within the last five years (excluding basal cell carcinoma) – History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis. – Patients who have undergone thoracotomy with pulmonary resection. – Any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period. – Current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit. – Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or MDI delivery systems. – Known symptomatic prostatic hypertrophy or bladder neck obstruction. – Patients with known narrow-angle glaucoma. – Current treatment with cromolyn sodium or nedocromil sodium. – Current treatment with antihistamines (H1 receptor antagonists). – Oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day. – Current use of β-blocker medication. – Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants. – 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 > 600mm3. – History of and/or active significant alcohol or drug abuse. – Concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit. – Changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit. – Inability to comply with the medication restrictions specified in Section 4.2 of the trial protocol
  • Gender Eligibility: All

    Minimum Age: 40 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Boehringer Ingelheim
    • Provider of Information About this Clinical Study
      • Sponsor

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