Dose response of umeclidinium administered once or twice daily in patients with COPD: a randomised cross-over studyReportar como inadecuado




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BMC Pulmonary Medicine

, 14:2

COPD and occupational lung disease

Abstract

BackgroundUmeclidinium bromide UMEC is an inhaled long-acting muscarinic antagonist in development for chronic obstructive pulmonary disease COPD.

MethodsThis was a multicentre, randomised, double-blind, placebo-controlled, three-way cross-over, incomplete block study to evaluate UMEC 15.6, 31.25, 62.5, and 125 μg administered once daily QD, and UMEC 15.6 μg and 31.25 μg administered twice daily BID, over 7 days in patients with COPD. Tiotropium was included as an open-label treatment arm. The primary efficacy endpoint was trough forced expiratory volume in 1 second FEV1 on Day 8. Secondary efficacy endpoints included weighted mean FEV1 over 0–24 hours after morning dosing on Day 7, and serial FEV1 at each time point over 24 hours after morning dosing on Day 7. Safety and pharmacokinetics were also examined.

ResultsOne hundred and sixty-three patients mean age 59.5 years, 52% female were randomised. Based on the population dose–response model of trough FEV1 data, the geometric mean potency ED50 of UMEC was 37 μg 95% confidence interval CI: 18, 57 with a predicted maximum intrinsic efficacy Emax at trough of 0.185 L 95% CI: 0.153, 0.218 after QD dosing. UMEC 125 μg QD demonstrated the greatest improvements in measure of lung function compared with doses of 62.5 μg and below. UMEC 125 μg QD exhibited more consistent increases in FEV1 from baseline across serial time points over 24 hours compared with other UMEC doses and tiotropium. Increases in FEV1 over 0–12 hours were similar to those observed over 12–24 hours after the second dose of UMEC was administered. UMEC was rapidly absorbed following inhaled dosing and eliminated from plasma. Adverse events, generally mild, were highest with UMEC 125 μg QD 18% compared with placebo 8%, tiotropium 4% and other UMEC doses 5–12%.

ConclusionsUMEC is a potent QD bronchodilator with geometric mean ED50 of 37 μg. A dose ordering over the range of UMEC 15.6–125 μg QD doses was observed, with UMEC 125 μg showing the greatest improvement in trough FEV1.

Trial registrationGlaxoSmithKline funded clinicaltrials.gov NCT01372410; GlaxoSmithKline study number AC4115321.

KeywordsChronic obstructive pulmonary disease COPD Long-acting bronchodilators Long-acting muscarinic antagonist LAMA Umeclidinium UMEC GSK573719 Electronic supplementary materialThe online version of this article doi:10.1186-1471-2466-14-2 contains supplementary material, which is available to authorized users.

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Autor: Alison Church - Misba Beerahee - Jean Brooks - Rashmi Mehta - Palvi Shah

Fuente: https://link.springer.com/



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