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)

NCT02242227 | Completed Phase 2

• 1 other identifier: 1184.10
• Study Type: interventional
• Target: 111
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Change in area under the curve for the time period 0 to 12 hours (AUC0-12h) of the forced expiratory volume in one second (FEV1)

  Pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10, and 12 hours post-dosing

Secondary Outcomes (23)

• Change in peak FEV1

  within 3 hours post-dosing

• Change in FEV1 AUC12-24h

  12, 14, 22, 23 and 24 hours post-dosing

• Change in FEV1 AUC0-24h

  Pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing

• Individual FEV1 measurements at each time point

  Pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing

• Change in forced vital capacity (FVC) AUC0-12h

  Pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10, and 12 hours post-dosing

Study Arms (3)

Salmeterol xinafoate

EXPERIMENTAL

25 μg Salmeterol inhalation powder administered via HandiHaler®

Drug: Salmeterol xinafoate; Drug: Placebo (Diskus®)

Serevent® Diskus®

ACTIVE COMPARATOR

50 μg Salmeterol (dry powder inhaler) administered via Diskus®

Drug: Serevent® Diskus®; Drug: Placebo (HandiHaler®)

Placebo

PLACEBO COMPARATOR

Drug: Placebo (HandiHaler®); Drug: Placebo (Diskus®)

Interventions

Salmeterol xinafoate DRUG

Salmeterol xinafoate

Serevent® Diskus® DRUG

Serevent® Diskus®

Placebo (HandiHaler®) DRUG

Placebo; Serevent® Diskus®

Placebo (Diskus®) DRUG

Placebo; Salmeterol xinafoate

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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®

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 17, 2014
• Study Start: September 1, 2005
• Primary Completion: February 1, 2006
• Last Updated: September 17, 2014

Record last verified: 2014-09