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

Colin Reisner, Leonardo M. Fabbri, Edward M. Kerwin, Charles Fogarty, Selwyn Spangenthal, Klaus F. Rabe, Gary T. Ferguson, Fernando J. Martinez, James F. Donohue, Patrick Darken, Earl St Rose, Chad Orevillo, Shannon Strom, Tracy Fischer, Michael Golden, Sarvajna Dwivedi

Research output: Contribution to journalArticle

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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.

LanguageEnglish (US)
Article number8
JournalRespiratory Research
Volume18
Issue number1
DOIs
StatePublished - Jan 6 2017

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Glycopyrrolate
Metered Dose Inhalers
Chronic Obstructive Pulmonary Disease
Suspensions
Technology
Safety
Area Under Curve
Placebos
Formoterol Fumarate
Pharmacokinetics
Dry Powder Inhalers
Muscarinic Antagonists
Forced Expiratory Volume
Cross-Over Studies

Keywords

  • Bronchodilators
  • Co-Suspension™ Delivery Technology
  • COPD
  • COPD maintenance
  • LABA
  • LAMA
  • Lung function
  • Metered dose inhaler

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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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. / Reisner, Colin; Fabbri, Leonardo M.; Kerwin, Edward M.; Fogarty, Charles; Spangenthal, Selwyn; Rabe, Klaus F.; Ferguson, Gary T.; Martinez, Fernando J.; Donohue, James F.; Darken, Patrick; St Rose, Earl; Orevillo, Chad; Strom, Shannon; Fischer, Tracy; Golden, Michael; Dwivedi, Sarvajna.

In: Respiratory Research, Vol. 18, No. 1, 8, 06.01.2017.

Research output: Contribution to journalArticle

Reisner, Colin ; Fabbri, Leonardo M. ; Kerwin, Edward M. ; Fogarty, Charles ; Spangenthal, Selwyn ; Rabe, Klaus F. ; Ferguson, Gary T. ; Martinez, Fernando J. ; Donohue, James F. ; Darken, Patrick ; St Rose, Earl ; Orevillo, Chad ; Strom, Shannon ; Fischer, Tracy ; Golden, Michael ; Dwivedi, Sarvajna. / 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. In: Respiratory Research. 2017 ; Vol. 18, No. 1.
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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, Co-Suspension™ Delivery Technology, COPD, COPD maintenance, LABA, LAMA, Lung function, Metered dose inhaler",
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T1 - 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

AU - Reisner,Colin

AU - Fabbri,Leonardo M.

AU - Kerwin,Edward M.

AU - Fogarty,Charles

AU - Spangenthal,Selwyn

AU - Rabe,Klaus F.

AU - Ferguson,Gary T.

AU - Martinez,Fernando J.

AU - Donohue,James F.

AU - Darken,Patrick

AU - St Rose,Earl

AU - Orevillo,Chad

AU - Strom,Shannon

AU - Fischer,Tracy

AU - Golden,Michael

AU - Dwivedi,Sarvajna

PY - 2017/1/6

Y1 - 2017/1/6

N2 - 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.

AB - 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.

KW - Bronchodilators

KW - Co-Suspension™ Delivery Technology

KW - COPD

KW - COPD maintenance

KW - LABA

KW - LAMA

KW - Lung function

KW - Metered dose inhaler

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U2 - 10.1186/s12931-016-0491-8

DO - 10.1186/s12931-016-0491-8

M3 - Article

VL - 18

JO - Respiratory Research

T2 - Respiratory Research

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