The efficacy and safety of combined tiotropium and olodaterol via the Respimat^® inhaler in patients with COPD: results from the Japanese sub-population of the Tonado^® studies

Abstract

Background

The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado^® 1 (NCT1431274) and 2 (NCT1431287) studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD.

Methods

In this Tonado^® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.

Results

Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0–3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg. Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg. SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies. Responses were similar in the overall population. Adverse-event incidence was generally balanced across treatment groups.

Conclusion

Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado^®.

Keywords:

• COPD
• bronchodilators
• maintenance treatment

Acknowledgments

This work was supported by Nippon Boehringer Ingelheim Co. Ltd. We would like to thank Shuhei Nakamura of Nippon Boehringer Ingelheim Co. Ltd for assistance with writing, and also Daisuke Kuroki and Mami Mori of Nippon Boehringer Ingelheim Co. Ltd for publication management and editorial support. Medical writing assistance was provided by Laura George, PhD, on behalf of Complete HealthVizion, and was contracted and compensated by Nippon Boehringer Ingelheim Co. Ltd.

Author contributions

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content of, and editorial decisions relating to the manuscript, were involved at all stages of development, and have approved the submitted manuscript. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors received no compensation related to the development of the manuscript. MI reports lecture fees from AstraZeneca, GlaxoSmithKline, Nippon Boehringer Ingelheim, and Novartis Pharma. HT reports lecture fees from AstraZeneca, GlaxoSmithKline, KYORIN Pharmaceutical, Meiji Seika Pharma, Nippon Boehringer Ingelheim, and Novartis Pharma. YF reports honoraria for consultancy from Eisai, Otsuka Pharmaceuticals, and Nippon Boehringer Ingelheim. AT, LG, LL, FV, and YZ are all employees of Boehringer Ingelheim. Interim findings from this analysis were presented at the Asian Pacific Society of Respirology Congress in Kuala Lumpur, Malaysia, December 3–6, 2015 as a poster presentation. The authors report no other conflicts of interest in this work.