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

Ichinose M, Takizawa A, Izumoto T, Tadayasu Y, Hamilton AL, Kunz C, Fukuchi Y - Int J Chron Obstruct Pulmon Dis (2015)

Bottom Line: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.A clear dose-response relationship was observed across all treatment groups.All doses of olodaterol were well tolerated, and no safety concerns were identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Background: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.

Objective: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD) olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD).

Methods: All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat Soft Mist inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1) after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC(0-3)), peak FEV1 from 0 hour to 3 hours (peak FEV1), and corresponding forced vital capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.

Results: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV1 and FEV1 AUC(0-3) compared to placebo were also significant (P<0.0001). A clear dose-response relationship was observed across all treatment groups. FVC responses (trough and FVC AUC(0-3)) supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified.

Conclusion: QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.

Trial registration: ClinicalTrials.gov: NCT00824382.

No MeSH data available.


Related in: MedlinePlus

Dose-normalized steady-state maximum concentrations (A) and AUC0–1 (B) of olodaterol.Note: Plasma concentrations after olodaterol 2 µg inhalation in most patients were below the limit of quantification; therefore, a gMean was not calculated.Abbreviations: gMean, geometric mean; Cmax,ss,norm, maximum measured concentration of olodaterol in plasma, steady-state, dose-normalized; AUC0–1,ss,norm, area under the curve from 0 hour to 1 hour, steady-state, dose-normalized.
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f6-copd-10-1673: Dose-normalized steady-state maximum concentrations (A) and AUC0–1 (B) of olodaterol.Note: Plasma concentrations after olodaterol 2 µg inhalation in most patients were below the limit of quantification; therefore, a gMean was not calculated.Abbreviations: gMean, geometric mean; Cmax,ss,norm, maximum measured concentration of olodaterol in plasma, steady-state, dose-normalized; AUC0–1,ss,norm, area under the curve from 0 hour to 1 hour, steady-state, dose-normalized.

Mentions: The distributions of dose-normalized systemic exposure parameters (Cmax,norm, AUC0–1,norm, Cmax,ss,norm, and AUC0–1,ss,norm) overlapped between the olodaterol 2 µg, 5 µg, and 10 µg groups; hence, systemic exposure was considered to increase proportionally within the dose range investigated (Cmax,ss,norm and AUC0–1,ss,norm in Figure 6).


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

Ichinose M, Takizawa A, Izumoto T, Tadayasu Y, Hamilton AL, Kunz C, Fukuchi Y - Int J Chron Obstruct Pulmon Dis (2015)

Dose-normalized steady-state maximum concentrations (A) and AUC0–1 (B) of olodaterol.Note: Plasma concentrations after olodaterol 2 µg inhalation in most patients were below the limit of quantification; therefore, a gMean was not calculated.Abbreviations: gMean, geometric mean; Cmax,ss,norm, maximum measured concentration of olodaterol in plasma, steady-state, dose-normalized; AUC0–1,ss,norm, area under the curve from 0 hour to 1 hour, steady-state, dose-normalized.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548739&req=5

f6-copd-10-1673: Dose-normalized steady-state maximum concentrations (A) and AUC0–1 (B) of olodaterol.Note: Plasma concentrations after olodaterol 2 µg inhalation in most patients were below the limit of quantification; therefore, a gMean was not calculated.Abbreviations: gMean, geometric mean; Cmax,ss,norm, maximum measured concentration of olodaterol in plasma, steady-state, dose-normalized; AUC0–1,ss,norm, area under the curve from 0 hour to 1 hour, steady-state, dose-normalized.
Mentions: The distributions of dose-normalized systemic exposure parameters (Cmax,norm, AUC0–1,norm, Cmax,ss,norm, and AUC0–1,ss,norm) overlapped between the olodaterol 2 µg, 5 µg, and 10 µg groups; hence, systemic exposure was considered to increase proportionally within the dose range investigated (Cmax,ss,norm and AUC0–1,ss,norm in Figure 6).

Bottom Line: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.A clear dose-response relationship was observed across all treatment groups.All doses of olodaterol were well tolerated, and no safety concerns were identified.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Background: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.

Objective: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD) olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD).

Methods: All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat Soft Mist inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1) after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC(0-3)), peak FEV1 from 0 hour to 3 hours (peak FEV1), and corresponding forced vital capacity (FVC) responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.

Results: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001). Mean increases in peak FEV1 and FEV1 AUC(0-3) compared to placebo were also significant (P<0.0001). A clear dose-response relationship was observed across all treatment groups. FVC responses (trough and FVC AUC(0-3)) supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified.

Conclusion: QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.

Trial registration: ClinicalTrials.gov: NCT00824382.

No MeSH data available.


Related in: MedlinePlus