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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: A clear dose-response relationship was observed across all treatment groups.All doses of olodaterol were well tolerated, and no safety concerns were identified.QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.

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

Mean plasma concentration–time profiles for olodaterol.Notes: Plasma concentrations after olodaterol 2 µg inhalation were too low to be quantified in most patients; therefore, mean plasma concentration profiles are not displayed.
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f5-copd-10-1673: Mean plasma concentration–time profiles for olodaterol.Notes: Plasma concentrations after olodaterol 2 µg inhalation were too low to be quantified in most patients; therefore, mean plasma concentration profiles are not displayed.

Mentions: Plasma concentrations after treatment with 2 µg of olodaterol were mostly below the limit of quantification (2 pg/mL). The mean plasma concentration–time profiles for olodaterol after treatment with 5 µg or 10 µg are presented in Figure 5. Peak plasma concentrations following inhalation (Cmax and Cmax at steady-state [Cmax,ss]) were observed within 20 minutes (tmax 0.283 hours and 0.300 hours; tmax at steady-state 0.333 hours and 0.300 hours for 5 µg and 10 µg of olodaterol, respectively; Tables 5 and 6). The apparent clearance at steady-state was 798 mL/min and 1,040 mL/min following administration of 5 µg and 10 µg of olodaterol, respectively. The accumulation ratios based on Cmax and area under the curve from 0 hour to 1 hour (AUC0–1) were low (1.59 to 1.77; Table 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)

Mean plasma concentration–time profiles for olodaterol.Notes: Plasma concentrations after olodaterol 2 µg inhalation were too low to be quantified in most patients; therefore, mean plasma concentration profiles are not displayed.
© Copyright Policy
Related In: Results  -  Collection

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

f5-copd-10-1673: Mean plasma concentration–time profiles for olodaterol.Notes: Plasma concentrations after olodaterol 2 µg inhalation were too low to be quantified in most patients; therefore, mean plasma concentration profiles are not displayed.
Mentions: Plasma concentrations after treatment with 2 µg of olodaterol were mostly below the limit of quantification (2 pg/mL). The mean plasma concentration–time profiles for olodaterol after treatment with 5 µg or 10 µg are presented in Figure 5. Peak plasma concentrations following inhalation (Cmax and Cmax at steady-state [Cmax,ss]) were observed within 20 minutes (tmax 0.283 hours and 0.300 hours; tmax at steady-state 0.333 hours and 0.300 hours for 5 µg and 10 µg of olodaterol, respectively; Tables 5 and 6). The apparent clearance at steady-state was 798 mL/min and 1,040 mL/min following administration of 5 µg and 10 µg of olodaterol, respectively. The accumulation ratios based on Cmax and area under the curve from 0 hour to 1 hour (AUC0–1) were low (1.59 to 1.77; Table 6).

Bottom Line: A clear dose-response relationship was observed across all treatment groups.All doses of olodaterol were well tolerated, and no safety concerns were identified.QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.

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