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)
Phase 2
Completed
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Registration Number
- NCT02242227
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 111
Inclusion Criteria
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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
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All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:
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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
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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)
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Male or female patients 40 years of age or older
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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)
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Patients must be able to perform technically acceptable pulmonary function tests during the study period as required in the protocol
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Patients must be able to inhale medication in a competent manner from the HandiHaler® 2 device and the Diskus® device
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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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo (Diskus®) - Salmeterol xinafoate Salmeterol xinafoate 25 μg Salmeterol inhalation powder administered via HandiHaler® Placebo Placebo (HandiHaler®) - Salmeterol xinafoate Placebo (Diskus®) 25 μg Salmeterol inhalation powder administered via HandiHaler® Serevent® Diskus® Serevent® Diskus® 50 μg Salmeterol (dry powder inhaler) administered via Diskus® Serevent® Diskus® Placebo (HandiHaler®) 50 μg Salmeterol (dry powder inhaler) administered via Diskus®
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Change in peak FEV1 within 3 hours post-dosing Peak FEV1 is defined as the maximum FEV1 obtained within the first three 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