A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease

Respir Res. 2017 Jan 6;18(1):8. doi: 10.1186/s12931-016-0491-8.

Abstract

Background: Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI).

Methods: This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD ( NCT01085045 ). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 7 relative to baseline FEV1. Secondary endpoints included pharmacokinetics and safety.

Results: GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV1 AUC0-12 after 7 days' treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated.

Conclusions: GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.

Trial registration: ClinicalTrials.gov NCT01085045 . Registered 9 March 2010.

Keywords: Bronchodilators; COPD; COPD maintenance; Co-Suspension™ Delivery Technology; LABA; LAMA; Lung function; Metered dose inhaler.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adult
  • Aged
  • Australia
  • Double-Blind Method
  • Drug Combinations
  • Equipment Design
  • Equipment Failure Analysis
  • Female
  • Formoterol Fumarate / administration & dosage*
  • Glycopyrrolate / administration & dosage*
  • Glycopyrrolate / adverse effects
  • Humans
  • Male
  • Metered Dose Inhalers*
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • New Zealand
  • Placebo Effect
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome
  • United States

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Drug Combinations
  • Muscarinic Antagonists
  • Glycopyrrolate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT01085045