Cardiovascular safety profile of a fixed-dose combination of glycopyrrolate and formoterol fumarate delivered via metered dose inhaler using co-suspension delivery technology.
Pulm Pharmacol Ther
; 49: 67-74, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-29567116
ABSTRACT
BACKGROUND:
Glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA), glycopyrrolate (GP), and the long-acting ß2-agonist (LABA), formoterol fumarate (FF), delivered via metered dose inhaler using innovative co-suspension delivery technology. Here we report the results of two studies that examined the cardiovascular safety of GFF MDI.METHODS:
The thorough QT (TQT) study was a Phase I, randomized, double-blind, single-dose, crossover study to assess GFF MDI 18/9.6 (Bevespi Aerosphere®), GFF MDI 144/38.4 and GP MDI 144⯵g, compared with placebo MDI and open-label moxifloxacin 400â¯mg (active control) in healthy volunteers (PT003009). The cardiovascular safety study in patients with chronic obstructive pulmonary disease (COPD) was a Phase IIb, randomized, multicenter, double-blind, 14-day dosing, parallel-group study to evaluate GFF MDI 36/9.6, GP MDI 36 and FF MDI 9.6⯵g compared with open-label FF dry powder inhaler (DPI; Foradil® Aerolizer®) 12⯵g, in patients with moderate-to-severe COPD (PT003003 [NCT01349803]).RESULTS:
Seventy healthy volunteers were randomized in the TQT study. GFF MDI 144/38.4, GFF MDI 18/9.6 and GP MDI 144⯵g all met the confidence interval-based criteria for negative QT prolongation potential. In the study in patients with COPD, 237 subjects were randomized and treated. GFF MDI 36/9.6, GP MDI 36, and FF MDI 9.6⯵g did not result in clinically meaningful changes from baseline in 24-h mean heart rate at Day 14 (primary endpoint) or in any of the other Holter monitoring endpoints at Day 14, compared with FF DPI 12⯵g.CONCLUSIONS:
No clinically significant effects on cardiovascular safety occurred at therapeutic or supratherapeutic doses of GFF MDI, apart from a small and transient increase in heart rate following supratherapeutic dose of GFF MDI 144/38.4⯵g. Furthermore, there were no unexpected safety findings reported in either healthy volunteers or patients with COPD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Método Duplo-Cego
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Sistemas de Liberação de Medicamentos
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Doença Pulmonar Obstrutiva Crônica
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Fumarato de Formoterol
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Glicopirrolato
Tipo de estudo:
Clinical_trials
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Etiology_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Pulm Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article