A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting β2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease

Abstract

ClinicalTrials.gov: NCT00452400.

Randomized, Double-Blind, Dose-Finding Study for Tiotropium when Added to Olodaterol, Administered via the Respimat® Inhaler in Patients with Chronic Obstructive Pulmonary Disease

“…This trial was part of a novel approach to dose finding with drug combinations, in which the dose response of each component within the FDC was explored to confirm whether it is the same as the dose response when used as monotherapy. The dose response of olodaterol alone was investigated in olodaterol dose-finding studies, which identified olodaterol 5 and 10 µg as the doses to be taken forward to the phase III trials [ 14 ], and the dose response of tiotropium monotherapy in the Respimat inhaler has been investigated [ 15 ], with 5 µg performing best and subsequently licensed in COPD. The present study was not powered to detect differences between different combined doses of tiotropium + olodaterol, but it was sufficient to identify dose ordering for FEV 1 responses for the dose combinations.…”

Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease

“…The findings from this study are broadly similar to another Phase II olodaterol dose-finding study (1222.5; NCT00452400) in non-Japanese patients with COPD, which provided evidence of the bronchodilator efficacy of 2 µg, 5 µg, 10 µg, and 20 µg of olodaterol QD over 24 hours. 10 Regarding the comparison of the systemic exposure of olodaterol, systemic exposure tended to be higher in the current study than in the non-Japanese study (ie, geometric mean C max,ss 5.92 pg/mL versus 4.02 pg/mL [5 µg], 13.1 pg/mL versus 7.13 pg/mL [10 µg], and AUC 0–1,ss 4.85 pg·h/mL versus 3.38 pg·h/mL [5 µg], 10.8 pg·h/mL versus 5.76 pg·h/mL [10 µg]). The main metabolic pathway of olodaterol clearance is related to uridine 5′-diphospho-g lucuronosyltransferase (UGT), for which racial difference in activity has not been reported.…”

“…With regard to efficacy, in the study with non-Japanese patients, the change from baseline in trough FEV 1 was 0.046, 0.082, and 0.109 with 2 µg, 5 µg, and 10 µg of olodaterol. 10 …”

“…This is the first study evaluating the effect of olodaterol in Japanese patients with COPD, and given its similarity to a recent study conducted in a Caucasian population (Study 1222.5), the study presented here will help to evaluate the ethnic sensitivity of the efficacy and safety of this therapy. 10 …”

Pharmacologic rationale underlying the therapeutic effects of tiotropium/olodaterol in COPD

“…Olodaterol exerts an efficacious, 24-hour-lasting protection against experimental ACh-induced bronchoconstriction in both guinea pigs and dogs. 38 Used by COPD patients once daily at dosages ranging from 2 to 20 µg, olodaterol elicits dose-dependent, significant increases in FEV 1 40 , 41 Two replicate, randomized, double-blind, placebo-controlled, and parallel-group phase III studies, carried out in patients with moderate to very severe COPD, have shown that olodaterol 5 and 10 µg significantly enhanced trough FEV 1 , and this bronchodilation was associated with an incidence of adverse events (AEs) comparable to that caused by placebo. 42 Such findings were further corroborated by other two replicate, multicenter studies, which also demonstrated that the improvements in lung function produced by olodaterol translated into symptomatic benefits for COPD patients.…”