A multicenter, randomized, double-blind dose-ranging study of glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler compared to the monocomponents and open-label tiotropium dry powder inhaler in patients with moderate-to-severe COPD.
This study formed part of the dose selection for a glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination formulated using novel Co-Suspension™ Delivery Technology and delivered via a metered dose inhaler (GFF MDI). The study aimed to confirm the optimal dose of GP to formulate with FF 9.6 μg in the fixed-dose combination product, GFF MDI.



This multicenter, randomized, double-blind, chronic-dosing, balanced incomplete block, crossover study (NCT01587079) compared five doses of GFF MDI (18/9.6, 9/9.6, 4.6/9.6, 2.4/9.6 and 1.2/9.6 μg, twice daily [BID]) with its monocomponents FF MDI 9.6 μg and GP MDI 18 μg (both BID) and open-label tiotropium (18 μg once daily) as the active control. The primary efficacy endpoint was change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1AUC0-12) on Day 7.



In total, 159 patients were randomized to treatment and 132 patients (52.2% male, mean age 62.8 years) were included in the intent-to-treat population. All doses of GFF MDI (except 1.2/9.6 μg) resulted in statistically significant improvements in FEV1AUC0-12versus monocomponents and open-label tiotropium. GFF MDI 18/9.6 μg consistently showing the greatest improvement over monocomponents and open-label tiotropium. Adverse events for each GFF MDI dose were similar versus GP MDI 18 μg, FF MDI 9.6 μg and open-label tiotropium.



These findings further support selection of GP 18 μg as the optimal dose to combine with FF MDI 9.6 μg for advancement into Phase III clinical trials of GFF MDI.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: DTashkin@mednet.ucla.edu.
Donald P
DP
Tashkin
Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Fernando J
FJ
Martinez
Servei de Pneumologia, Institut del Tòrax, Hospital Clínic-IDIBAPS-CIBERES, University of Barcelona, Barcelona, Spain.
Roberto
R
Rodriguez-Roisin
Spartanburg Medical Research, Spartanburg, SC, USA.
Charles
C
Fogarty
Pulmonary Associates, Phoenix, AZ, USA.
Mark
M
Gotfried
Clinical Research of Rock Hill, Rock Hill, SC, USA.
Michael
M
Denenberg
New Horizons Clinical Research, Cincinnati, OH, USA.
Gregory
G
Gottschlich
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
James F
JF
Donohue
Pearl Therapeutics Inc., Morristown, NJ, USA.
Chad
C
Orevillo
Pearl Therapeutics Inc., Morristown, NJ, USA.
Patrick
P
Darken
Pearl Therapeutics Inc., Morristown, NJ, USA.
Earl
E
St Rose
Pearl Therapeutics Inc., Durham, NC, USA.
Shannon
S
Strom
Pearl Therapeutics Inc., Durham, NC, USA.
Tracy
T
Fischer
Pearl Therapeutics Inc., Durham, NC, USA.
Michael
M
Golden
Pearl Therapeutics Inc., Morristown, NJ, USA.
Colin
C
Reisner
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D058995:Dry Powder Inhalers / Q000379:methods*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers / Q000706:statistics & numerical data*; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D016896:Treatment Outcome
D058666:Adrenergic beta-2 Receptor Agonists; D018680:Cholinergic Antagonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D006024:Glycopyrrolate; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
Bronchodilators; COPD maintenance therapy; Co-Suspension™ Delivery Technology; Fixed-dose combinations; LABA; LAMA