- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT02238106
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)
A Single Dose, Placebo-controlled, Randomized, Double-blind, Double-dummy, Crossover Efficacy, Pharmacokinetics and Safety Comparison of Salmeterol Inhalation Powder (12.5 μg, 25 μg and 50 Salmeterol), Administered as the Xinafoate Salt From Hard Polyethylene Capsules Via the HandiHaler® 2, and Serevent® Diskus® (50 μg Salmeterol) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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.
Studieoversigt
Status
Betingelser
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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 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. See exclusion criterion No 6
- 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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Salmeterol inhalation powder, medium dose
administered via HandiHaler®
|
|
|
Aktiv komparator: Salmeterol inhalation powder, low dose
administered via HandiHaler®
|
|
|
Aktiv komparator: Salmeterol inhalation powder, high dose
administered via HandiHaler®
|
|
|
Aktiv komparator: Serevent® Diskus®
administered via Diskus®
|
|
|
Placebo komparator: Placebo
administered via Diskus® or HandiHaler®
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
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)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in peak FEV1
Tidsramme: within 3 hours post-dosing
|
Peak FEV1 is defined as the maximum FEV1 obtained within the first three hours post dosing
|
within 3 hours post-dosing
|
|
Change in peak forced vital capacity (FVC)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
Change in FVC AUC0-12h
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
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
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
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
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
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)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
Cmax (maximum measured concentration of the analyte in plasma)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
λz (terminal rate constant in plasma)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
t½ (terminal half-life of the analyte in plasma)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
MRTih (mean residence time of the analyte in the body after inhalational administration)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Tidsramme: pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
pre-dose and 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
|
|
|
Aet1-t2 (amount of analyte that is eliminated in urine from the time interval t1 to t2)
Tidsramme: 0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
|
|
fet1-t2 (fraction of administered drug excreted unchanged in urine from time point t1 to t2)
Tidsramme: 0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
|
|
CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)
Tidsramme: 0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
0 to 3h 5min, from 3h 5min to 6h 5min, and from 6h 5min to 8h 5min after administration
|
|
|
Antal patienter med bivirkninger
Tidsramme: op til 36 dage
|
op til 36 dage
|
Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Luftvejssygdomme
- Lungesygdomme
- Lungesygdomme, obstruktiv
- Lungesygdom, kronisk obstruktiv
- Lægemidlers fysiologiske virkninger
- Adrenerge midler
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Autonome agenter
- Agenter fra det perifere nervesystem
- Adrenerge agonister
- Bronkodilatatorer
- Anti-astmatiske midler
- Respiratoriske midler
- Adrenerge beta-2-receptoragonister
- Adrenerge beta-agonister
- Salmeterol Xinafoate
Andre undersøgelses-id-numre
- 1184.12
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