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Effect of once-daily fluticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study.
Boscia, Joseph A; Pudi, Krishna K; Zvarich, Michael T; Sanford, Lisa; Siederer, Sarah K; Crim, Courtney.
Afiliação
  • Boscia JA; CU Pharmaceutical Research, Union, South Carolina 29379, USA. joseph@cupharmresearch.com
Clin Ther ; 34(8): 1655-66.e5, 2012 Aug.
Article em En | MEDLINE | ID: mdl-22789766
ABSTRACT

BACKGROUND:

Available inhaled corticosteroid/long-acting ß(2)-agonist combinations for chronic obstructive pulmonary disease (COPD) require twice-daily administration. The combination of fluticasone furoate (FF) and vilanterol (VI) FF/VI is being developed in a novel dry powder inhaler for the treatment of COPD and asthma with the potential for once-daily dosing. Results from Phase II studies have shown clinically and statistically significant improvements over placebo in trough (24-hour postdose) forced expiratory volume in 1 second (FEV(1)) after once-daily dosing with FF or VI (VI concurrently with an inhaled corticosteroid) in asthma and VI in COPD.

OBJECTIVES:

This Phase III, multicenter, randomized, double-blind, placebo-controlled study was designed based on guidance from drug regulators with the goal of evaluating the 24-hour spirometric effect of once-daily FF/VI in patients with COPD.

METHODS:

Patients (aged ≥40 years) who completed a 2-week placebo run-in period were randomized to 1 of 18 three-course sequences of placebo and 2 of 3 dose combinations of FF/VI (50/25 µg, 100/25 µg, and 200/25 µg), dosed once daily in the morning. Each 28-day treatment period was separated by a 2-week, single-blind, placebo washout period. The primary end point was time-adjusted (weighted mean) 0 to 24-hour FEV(1) (AUC) at the end of each 28-day treatment period (period days 28-29). Safety profile assessments included incidence of adverse events (AEs) (defined according to the Medical Dictionary for Regulatory Activities), 12-lead ECG outputs, vital signs (pulse rate, diastolic and systolic blood pressure) and clinical laboratory assessments (including fasting serum glucose and potassium) and 24-hour serum cortisol. The pharmacokinetics of FF and VI were assessed at the end of each 28-day treatment period with FF/VI.

RESULTS:

Eighty-seven patients were screened; 54 completed run-in and were randomized to double-blind treatment. The mean patient age was 57.9 years, and 46% were male. The majority of patients were current smokers (83%) and were receiving short-acting ß(2)-agonists within the 3 months before screening (63%). All 3 strengths of once-daily FF/VI demonstrated significantly higher 0 to 24-hour (period days 28-29) change from period baseline weighted mean FEV(1) than placebo adjusted mean improvements from placebo in FEV(1) for FF/VI were 220 to 236 mL (all, P < 0.001). Improvements versus placebo in change from period baseline serial FEV(1) measures were observed at each time-point and with each strength of FF/VI over the 0 to 25-hour period (period days 28-29), indicating sustained bronchodilation. The overall incidence of on-treatment AEs was low (10%-12% with FF/VI; 4% with placebo); 2 serious AEs were reported during washout periods (1 AE after FF/VI 50/25 µg and 1 AE after placebo) but neither was considered treatment related. No serious AEs were reported during the treatment periods or during the follow-up period. No clinically or statistically significant differences from placebo were reported for serum glucose or potassium. No significant effects on vital signs, ECG, or 24-hour serial serum cortisol were reported. The extent of systemic exposure to FF and VI at steady state was low for all strengths of FF/VI.

CONCLUSIONS:

FF/VI inhaled once daily in the morning for 28 days produced significant improvements in pulmonary function with a prolonged (>24 hours') duration of action in this population of patients with COPD. The combination was well tolerated. ClinicalTrials.gov identifier NCT01072149.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Álcoois Benzílicos / Broncodilatadores / Clorobenzenos / Doença Pulmonar Obstrutiva Crônica / Agonistas de Receptores Adrenérgicos beta 2 / Glucocorticoides / Androstadienos / Pulmão Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged País como assunto: America do norte Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Álcoois Benzílicos / Broncodilatadores / Clorobenzenos / Doença Pulmonar Obstrutiva Crônica / Agonistas de Receptores Adrenérgicos beta 2 / Glucocorticoides / Androstadienos / Pulmão Tipo de estudo: Clinical_trials / Diagnostic_studies / Guideline / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged País como assunto: America do norte Idioma: En Ano de publicação: 2012 Tipo de documento: Article