Efficacy, Pharmacokinetics and Safety Comparison of Salmeterol Inhalation Powder Administered Via the HandiHaler® 2 and Serevent® Diskus® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Efficacy, Pharmacokinetics and Safety Comparison of Salmeterol Inhalation Powder Administered Via the HandiHaler® 2 and Serevent® Diskus® in Patients With Chronic Obstructive Pulmonary Disease (COPD)
The primary objective of this trial was to establish non-inferiority of lung function
 response to 25 μg salmeterol, administered as the xinafoate salt, in an inhalation powder
 delivered from hard polyethylene (PE) capsules via the HandiHaler® 2 compared to Serevent®
 Diskus® (salmeterol 50 μg, administered as the xinafoate salt) following single dose
 inhalation in patients with COPD.

 The secondary objectives were to characterize the pharmacokinetics of salmeterol inhalation
 powder delivered by HandiHaler® 2 from the PE hard capsule and salmeterol xinafoate delivered
 by Serevent® Diskus®, and to compare the safety of the two pharmaceutical forms.
Inclusion Criteria:

 -  All patients must sign an informed consent consistent with International Conference on
 Harmonization Good Clinical Practice (ICH-GCP) guidelines and local legislations prior
 to any study-related procedures, which includes medication washout and restrictions

 -  All patients must have a diagnosis of chronic obstructive pulmonary disease and must
 meet the following spirometric criteria:

 -  Patients must have relatively stable* airway obstruction with a pre-dose FEV1 ≤
 60% of predicted normal and FEV1 ≤ 70% of FVC at Visits 1 and 2.

 -  *The enrolment of patients who have had an exacerbation within six weeks
 prior to planned study entry should be postponed

 -  At Visit 1, patients must demonstrate an improvement in FEV1 of ≥ 12% over the
 pre-bronchodilator value 45 minutes after inhalation of 4 puffs of 100 μg salbutamol
 (Sultanol® MDI)

 -  Male or female patients 40 years of age or older

 -  Patients must be current or ex-smokers with a smoking history of more than 10
 pack-years ((Patients who have never smoked cigarettes must be excluded)

 -  Patients must be able to perform technically acceptable pulmonary function tests
 during the study period as required in the protocol

 -  Patients must be able to inhale medication in a competent manner from the HandiHaler®
 2 device and the Diskus® device

 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 a recent history (i.e., six months or less) of myocardial infarction

 -  Patients who have been hospitalized for heart failure (New York Heart Association
 (NYHA) class III or IV) within the past year

 -  Patients with any unstable or life threatening cardiac arrhythmia or cardiac
 arrhythmia requiring intervention or a change in drug therapy within the past year

 -  Patients with malignancy for which the patient has undergone resection, radiation
 therapy or chemotherapy within the last five years. Patients with treated basal cell
 carcinoma are allowed

 -  Patients with a history of asthma, allergic rhinitis or atopy or who have a total
 blood eosinophil count ≥600/mm3

 -  Patients with a history of life threatening pulmonary obstruction, or a history of
 cystic fibrosis or clinically evident bronchiectasis

 -  Patients with known active tuberculosis

 -  Patients with significant alcohol or drug abuse within the past two years

 -  Patients who have undergone thoracotomy with pulmonary resection. Patients with a
 history of thoracotomy for other reasons should be evaluated as per exclusion
 criterion No. 1

 -  Patients who have completed a pulmonary rehabilitation program in the six weeks prior
 to the Screening Visit (Visit 1) or patients who are currently in a pulmonary
 rehabilitation program that will not be maintained throughout the duration of the
 study

 -  Patients who regularly use daytime oxygen therapy for more than one hour per day and
 in the investigator's opinion will be unable to abstain from the use of oxygen therapy

 -  Patients who are being treated with antihistamines (H1 receptor antagonists),
 antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic
 conditions

 -  Patients who have been treated with cromolyn sodium or nedocromil sodium within one
 month prior to Visit 1 or during the run-in period

 -  Patients using 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 prednisone
 per day or 20 mg every other day

 -  Patients with known hypersensitivity to beta-adrenergics, lactose or any other
 components of the inhalation capsule delivery system or the Diskus®

 -  Pregnant or nursing women or women of childbearing potential not using a medically
 approved means of contraception for the previous three months (i.e. oral
 contraceptives, intrauterine devices, diaphragm or subdermal implants, e.g.:
 Norplant®)

 -  Patients who have taken an investigational drug within one month or six half lives
 (whichever is greater) prior to Visit 1

 -  Patients who have been treated with oral beta-adrenergics within one month prior to
 Visit 1 or during the run-in period

 -  Patients who have been treated with theophylline preparations within one month prior
 to Visit 1 or during the run-in period

 -  Patients who have been treated with the long-acting anticholinergic tiotropium
 (Spiriva®) within one month prior to Visit 1 or during the run-in period

 -  Patients with any respiratory infections in the six weeks prior to the Screening Visit
 (Visit 1) or during the run-in period. In the case of a respiratory infection during
 the run-in period the latter may be extended up to six weeks

 -  Patients who are currently participating in another study