Pilot Study Comparing Tiotropium (Spiriva) to Salmeterol (Serevent) Plus Fluticasone (Flixotide) in Chronic Obstructive Pulmonary Disease (COPD)

This is a six-week, multi-centre, randomised, double-blind, triple-dummy, parallel group pilot study to compare the bronchodilator efficacy and safety of the long-acting bronchodilator tiotropium (Spiriva, 18 µg q.d.) to the free combination of fluticasone (Flixotide, 250 µg b.i.d.) and salmeterol (Serevent, 50 µg b.i.d.) in patients with COPD.

Following an initial screening at Visit 1, subjects will enter a two-week run-in period during which they will record daily rescue salbutamol use in the Patient Daily Diary Card. At Visit 1, pre-dose and post-bronchodilator pulmonary function tests (PFT) will be measured. Four inhalations of ipratropium (20 µg per puff) and four inhalations of salbutamol (100 µg per puff) will be administered 60 minutes prior to obtaining post-bronchodilator PFT measurement.

At Visit 2, a pre-dose PFT will be performed prior to first administration of trial medication. Treatment with blinded study medication (tiotropium or fluticasone + salmeterol) will start in the morning of Visit 2 (Day 1). After three weeks of treatment, at Visit 3 (Day 22), pre-dose FEV1 and FVC will be measured, patient compliance checked and a re-supply of study medication dispensed. After six weeks of treatment, at Visit 4 (Day 43), a 12 hour profile of PFTs will be obtained.

Study Hypothesis:

As this is a pilot trial to investigate the efficacy and safety of tiotropium (18 µg q.d.) as compared to the free combination of fluticasone (250 µg b.i.d.) and salmeterol (50 µg b.i.d.), no formal hypothesis testing will be performed. However, the underlying hypothesis for this trial is that tiotropium is superior to the free combination with respect to the primary efficacy endpoint FEV1AUC0-12 (area under the curve for the time period 0 to 12 hours).

Comparison(s):

At least 100 male or female outpatients with clinical and spirometric evidence of chronic obstructive pulmonary disease (COPD) will be entered in this study. Patients will be randomly assigned to receive either tiotropium inhalation capsules 18 µg q.d., or salmeterol 50 µg oral inhalation b.i.d. in free combination with fluticasone 250 µg oral inhalation b.i.d. in a double-blind triple-dummy fashion.

Inclusion criteria

• All patients must have a diagnosis of chronic obstructive pulmonary disease according to the GOLD criteria and must meet the following spirometric criteria:

• Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 < 80% of predicted normal and FEV1/FVC < 70% at Visit 1, and a pre-dose FEV1 < 65% predicted at Visit 2.
• Male or female patients 40 years of age or older. There is no upper age limit.
• Patients must be current or ex-smokers with a smoking history of more than 10 pack-years.

Exclusion criteria

• Patients with significant diseases other than COPD.
• Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count more than or equal to 600/mm3.
• Patients who have been treated with commercially available tiotropium (Spiriva®).