Salmeterol Inhalation Powder Administered as the Xinafoate Salt From Hard Polyethylene Capsules Via the HandiHaler® 2, and Serevent® Diskus® in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT02238106 | Completed Phase 2

• 1 other identifier: 1184.12
• Study Type: interventional
• Target: 136
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this trial was to establish non-inferiority of lung function response to two doses \[25 μg (1 capsule) and 50 μg (2 capsules of 25 μg)\] 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. A hard capsule with half the strength (12.5 μg) was included to investigate a dose ordering effect. The secondary objectives were to characterize the pharmacokinetics of salmeterol inhalation powder delivered by HandiHaler® 2 from the PE hard capsule(s) and salmeterol xinafoate delivered by Serevent® Diskus®, and to compare the safety of the different pharmaceutical forms and/or doses.

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 (19)

• Change in peak FEV1

  within 3 hours post-dosing

• Change in peak forced vital capacity (FVC)

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

• Change in FVC AUC0-12h

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

• Individual FEV1 measurements at each time point

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

• Individual FVC measurements at each time point

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

Study Arms (5)

Salmeterol inhalation powder, medium dose

EXPERIMENTAL

administered via HandiHaler®

Drug: Salmeterol medium dose; Drug: Placebo HandiHaler®; Drug: Placebo Diskus®

Salmeterol inhalation powder, low dose

ACTIVE COMPARATOR

administered via HandiHaler®

Drug: Salmeterol low dose; Drug: Placebo HandiHaler®; Drug: Placebo Diskus®

Salmeterol inhalation powder, high dose

ACTIVE COMPARATOR

administered via HandiHaler®

Drug: Salmeterol high dose; Drug: Placebo Diskus®

Serevent® Diskus®

ACTIVE COMPARATOR

administered via Diskus®

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

Placebo

PLACEBO COMPARATOR

administered via Diskus® or HandiHaler®

Drug: Placebo HandiHaler®; Drug: Placebo Diskus®

Interventions

Salmeterol medium dose DRUG

Salmeterol inhalation powder, medium dose

Salmeterol low dose DRUG

Salmeterol inhalation powder, low dose

Salmeterol high dose DRUG

Salmeterol inhalation powder, high dose

Serevent® Diskus® DRUG

Serevent® Diskus®

Placebo HandiHaler® DRUG

Placebo; Salmeterol inhalation powder, low dose; Salmeterol inhalation powder, medium dose; Serevent® Diskus®

Placebo Diskus® DRUG

Placebo; Salmeterol inhalation powder, high dose; Salmeterol inhalation powder, low dose; Salmeterol inhalation powder, medium dose

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 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 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®)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Related Links

• Related Info

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 11, 2014
• First Posted: September 12, 2014
• Study Start: September 1, 2005
• Primary Completion: February 1, 2006
• Last Updated: September 12, 2014

Record last verified: 2014-09