Clinical Trials/NCT02242227

NCT02242227

Completed

Phase 2

A Single Dose, Placebo-controlled, Randomized, Double-blind, Double-dummy, Crossover Efficacy, Pharmacokinetics and Safety Comparison of Salmeterol Inhalation Powder (25 μg Salmeterol), Administered as the Xinafoate Salt From a Hard Polyethylene Capsule Via the HandiHaler® 2, and Serevent® Diskus® (50 μg Salmeterol) in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Boehringer Ingelheim0 sites111 target enrollmentSeptember 2005

ConditionsPulmonary Disease, Chronic Obstructive

InterventionsSalmeterol xinafoate Placebo (Diskus®)Serevent® Diskus®Placebo (HandiHaler®)

DrugsSalmeterol xinafoate Serevent® Diskus®Placebo (HandiHaler®)Placebo (Diskus®)

Overview

Phase: Phase 2
Intervention: Salmeterol xinafoate
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim
Enrollment: 111
Primary Endpoint: 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)
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 2005

End Date

February 2006

Last Updated

11 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

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
•\*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

Arms & Interventions

Salmeterol xinafoate

25 μg Salmeterol inhalation powder administered via HandiHaler®

Intervention: Salmeterol xinafoate

Salmeterol xinafoate

25 μg Salmeterol inhalation powder administered via HandiHaler®

Intervention: Placebo (Diskus®)

Serevent® Diskus®

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

Intervention: Serevent® Diskus®

Serevent® Diskus®

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

Intervention: Placebo (HandiHaler®)

Placebo

Intervention: Placebo (HandiHaler®)

Placebo

Intervention: Placebo (Diskus®)

Outcomes

Primary Outcomes

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)

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

Secondary Outcomes

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)
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
Aet1-t2 (amount of analyte that is eliminated in urine from the time interval t1 to t2)(0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration)
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)
Change in FVC 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 FVC 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)
tmax (time from dosing to the maximum concentration of the analyte in plasma)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
λz (terminal rate constant in plasma)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
t½ (terminal half-life of the analyte in plasma)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
MRTih (mean residence time of the analyte in the body after inhalational administration)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2; a time interval from 0 - 8 h is appropriate)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
Cmax (maximum measured concentration of the analyte in plasma)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)(0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration)
Change in peak FVC(Pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing)
Change in FVC AUC12-24h(12, 14, 22, 23 and 24 hours post-dosing)
Number of patients with adverse events(up to 23 days)
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)(pre-dose and 2, 5, 10, 17, 25, 40 minutes, and 1h 5min, 1h 35 min, 3h 5min, 6h 5min, and 8h 5 min following drug administration)
fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)(0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration)