Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients.
NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD. This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (>or=40 years; smoking history >or=10 pack-years) with stable moderate-to-severe COPD (post-bronchodilator FEV(1) >or= 30% and <80% predicted, FEV(1)/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 microg, placebo, or tiotropium 18 microg once-daily for 7 days. The primary endpoint was mean trough (23-24 h post-dose) FEV(1) on Day 7. Secondary endpoints included mean trough FEV(1) on Day 1, and FEV(1) and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV(1) 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV(1) on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 microg, 100 microg and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV(1) was significantly higher (p < 0.05) with NVA237 50 and 100 microg versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated. NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852).
Verkindre
C
C
Hopital de Bethune, Beuvry, France. cverkindre@ch-bethune.fr
Fukuchi
Y
Y
Flémale
A
A
Takeda
A
A
Overend
T
T
Prasad
N
N
Dolker
M
M
D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D012602:Scopolamine Derivatives; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide