Pharmacokinetics and safety of a single dose of the novel LAMA/LABA fixed-dose combination of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler, formulated using co-suspension delivery technology, in Japanese healthy subjects

Pulm Pharmacol Ther. 2018 Dec:53:33-38. doi: 10.1016/j.pupt.2018.09.005. Epub 2018 Sep 13.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) causes significant mortality in Japan. GFF MDI is a long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination of glycopyrronium (GP) and formoterol fumarate dihydrate (FF), delivered by a metered dose inhaler (MDI) using co-suspension delivery technology, for the long-term maintenance treatment of COPD.

Methods: This randomized, Phase I, single-dose, four-treatment, four-period, crossover study (NCT02196714) examined the pharmacokinetic (PK) and safety profile of two doses of GFF MDI (28.8 μg/10 μg and 14.4 μg/10 μg) and two doses of GP MDI (28.8 μg and 14.4 μg), both formulated using co-suspension delivery technology, in healthy Japanese subjects (18-45 years of age). PK parameters included area under the curve (AUC) from 0 to 12 h (AUC0-12), AUC from 0 to the time of the last measurable plasma concentration, maximum observed plasma concentration (Cmax), and time to Cmax. Safety was monitored throughout the study.

Results: Plasma GP profiles were comparable between GFF MDI and GP MDI formulations containing the same GP dose. Increases in GP AUC0-12 and Cmax were generally dose proportional from 14.4 to 28.8 μg after administration of either formulation.

Conclusions: The addition of FF 10 μg to GP MDI 28.8 μg or 14.4 μg in a fixed-dose combination did not appreciably alter the PK of GP, nor did an increase in GP dose from 14.4 μg to 28.8 μg in a fixed-dose combination with FF 10 μg appreciably alter the PK of formoterol. Both formulations of GFF MDI and GP MDI were well tolerated in healthy Japanese subjects. Data from this study support further evaluation of GFF MDI in Japanese patients with COPD.

Keywords: Chronic obstructive pulmonary disease; Co-suspension delivery technology; GFF MDI; LAMA/LABA; Pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Area Under Curve
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / pharmacokinetics
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Drug Delivery Systems
  • Female
  • Formoterol Fumarate / administration & dosage*
  • Formoterol Fumarate / adverse effects
  • Formoterol Fumarate / pharmacokinetics
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Glycopyrrolate / pharmacokinetics
  • Humans
  • Japan
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage*
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / pharmacokinetics
  • Suspensions
  • Young Adult

Substances

  • Bronchodilator Agents
  • Drug Combinations
  • Muscarinic Antagonists
  • Suspensions
  • Glycopyrrolate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT02196714