Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2014 Oct 14:9:1133-44.
doi: 10.2147/COPD.S72482. eCollection 2014.

Efficacy and safety of combining olodaterol Respimat(®) and tiotropium HandiHaler(®) in patients with COPD: results of two randomized, double-blind, active-controlled studies

Richard ZuWallack  1 , Lisa Allen  2 , Gemzel Hernandez  2 , Naitee Ting  2 , Roger Abrahams  3
Affiliations
Randomized Controlled Trial

Efficacy and safety of combining olodaterol Respimat(®) and tiotropium HandiHaler(®) in patients with COPD: results of two randomized, double-blind, active-controlled studies

Richard ZuWallack et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD). We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.

Methods: Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat(®)) combined with tiotropium 18 μg once daily (via HandiHaler(®)) versus tiotropium 18 μg once daily (via HandiHaler(®)) combined with placebo (via Respimat(®)) in patients with moderate to severe COPD. Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials). A key secondary end point was health status by St George's Respiratory Questionnaire (SGRQ) total score (combined data set).

Results: Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points. These effects translated to improvements in SGRQ total scores (treatment difference -1.85; P<0.0001). The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.

Conclusion: These studies demonstrated that olodaterol (Respimat(®)) and tiotropium (HandiHaler(®)) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.

Keywords: bronchodilator; long-acting beta2-agonist; long-acting muscarinic antagonist; olodaterol Respimat®; tiotropium HandiHaler®.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Design of ANHELTO 1 and ANHELTO 2.
Figure 2
Figure 2
Patient disposition (A) ANHELTO 1; (B) ANHELTO 2. Abbreviation: AE, adverse event.
Figure 3
Figure 3
FEV1 on day 1 in (A) ANHELTO 1; (B) ANHELTO 2, and at week 12 in (C) ANHELTO 1; (D) ANHELTO 2. Abbreviations: FEV1, forced expiratory volume in 1 second; h, hours.
Figure 4
Figure 4
FEV1 AUC0–3 response to treatment in (A) ANHELTO 1; (B) ANHELTO 2. Notes: ****P<0.0001 (olodaterol + tiotropium versus tiotropium + placebo); n=1,132 (ANHELTO 1), n=1,135 (ANHELTO 2). Abbreviation: FEV1 AUC0–3, area under the curve from 0–3 hours of forced expiratory volume in 1 second.
Figure 5
Figure 5
Trough FEV1 response to treatment in (A) ANHELTO 1; (B) ANHELTO 2. Notes: **P<0.01 (olodaterol + tiotropium versus tiotropium + placebo); n=1,132 (ANHELTO 1), n=1,135 (ANHELTO 2). Abbreviation: FEV1, forced expiratory volume in 1 second.
See this image and copyright information in PMC

References

    1. Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179–191. - PubMed
    1. National Heart, Lung, and Blood Institute [homepage on the Internet] NHLBI Factbook. 4. Disease Statistics [updated 2006] [Accessed March 21, 2014]. Available from: http://www.nhlbi.nih.gov/about/factbook-06/chapter4data.htm.
    1. Global Initiative for Chronic Obstructive Lung Disease [homepage on the Internet] Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. [Accessed March 5, 2014]. Updated 2013 [updated 2013]. Available from: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2013_Feb20.pdf.
    1. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19(2):217–224. - PubMed
    1. O’Donnell DE, Flüge T, Gerken F, et al. Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J. 2004;23(6):832–840. - PubMed

Publication types

MeSH terms

Associated data