Abstract

BackgroundBatefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β2-adrenoceptor agonist pharmacology. This Phase II, randomized, placebo-controlled, double-blind study evaluated the safety and tolerability of BAT 300 μg with fluticasone furoate (FF) 100 μg administered via the ELLIPTA inhaler (BAT/FF 300/100).MethodsSubjects with stable chronic obstructive pulmonary disease were randomized 2:1 to receive BAT/FF 300/100 or placebo once daily for 6 weeks. The primary endpoint was change from baseline in 0–4-h weighted mean (WM) heart rate (HR, measured by electrocardiogram [ECG]) on Day 42. Other endpoints included WM and maximum 0–4-h corrected QT interval (ECG on Days 1, 28, and 42), HR measured by Holter monitoring (Day 42), and standard safety assessments. Study protocol was approved by an Investigational Review Board.ResultsSixty-two patients were randomized and received ≥1 dose of study medication (BAT/FF 300/100 n = 42; placebo n = 20). Mean age was 62.5 years (standard deviation [SD] 8.17). Study completion rates were 83% (BAT/FF 300/100) and 100% (placebo). Screening mean (SD) post-bronchodilator percentage-predicted forced expiratory volume in 1 s was 57.57 (11.42) in the BAT/FF 300/100 group and 55.68 (14.03) in the placebo group. BAT/FF 300/100 was non-inferior to placebo for the primary endpoint, treatment difference: − 2.2 beats per minute (bpm), 95% confidence interval [CI]: − 6.2, 1.7). There were no clinically relevant differences between treatment groups in WM or maximum 0–4-h corrected QT interval, or mean HR based on Holter monitoring on Day 42 (BAT/FF 300/100: 76.3 bpm [SD 11.38]; placebo: 84.8 bpm [SD 9.87]). Adverse events (AEs) occurred in 38% (BAT/FF 300/100) and 35% (placebo) of patients. AEs in ≥2 subjects with BAT/FF 300/100 were dysgeusia (10%), diarrhea (7%), nasopharyngitis (7%), and cough (5%). AEs leading to discontinuation occurred in two subjects who received BAT/FF 300/100: post-treatment severe pneumonia (serious AE) and non-serious AEs of moderate vomiting and severe gastroenteritis; both were not considered drug-related. No deaths occurred.ConclusionsSix weeks of BAT/FF 300/100 treatment was non-inferior to placebo for change from baseline in HR, with no new clinically relevant general or cardiovascular safety signals.Trial registrationClinicaltrials.gov: NCT02573870 (submitted October 12, 2015).

Highlights

  • Batefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β2-adrenoceptor agonist pharmacology

  • Six weeks of BAT/fluticasone furoate (FF) 300/100 treatment was non-inferior to placebo for change from baseline in heart rate (HR), with no new clinically relevant general or cardiovascular safety signals

  • Subject demographics and baseline characteristics were generally similar and balanced between the groups, with some exceptions; for example, there was a higher proportion of smokers at baseline in the placebo group compared with the BAT/FF 300/100 group (Table 1)

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Summary

Introduction

Batefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β2-adrenoceptor agonist pharmacology. This Phase II, randomized, placebo-controlled, double-blind study evaluated the safety and tolerability of BAT 300 μg with fluticasone furoate (FF) 100 μg administered via the ELLIPTA inhaler (BAT/FF 300/ 100). Inhaled bronchodilator therapy with long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are recommended for the maintenance treatment of most patients with COPD [1, 2]. There has been increasing interest in triple therapy (LABA/LAMA/ICS) to provide further improvements for patients with COPD who are not adequately controlled with dual combination therapy [4, 5]. Fluticasone furoate (FF) is a potent once-daily ICS, currently available in combination with the LABA vilanterol (VI) as a treatment for patients with COPD in the United States (US) and Europe, and as triple therapy with VI and umeclidinium, a LAMA, as maintenance treatment for patients with COPD in the US

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