Donald P Tashkin1, Fernando J Martinez2, Roberto Rodriguez-Roisin3, Charles Fogarty4, Mark Gotfried5, Michael Denenberg6, Gregory Gottschlich7, James F Donohue8, Chad Orevillo9, Patrick Darken9, Earl St Rose9, Shannon Strom10, Tracy Fischer10, Michael Golden10, Colin Reisner9. 1. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: DTashkin@mednet.ucla.edu. 2. Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 3. Servei de Pneumologia, Institut del Tòrax, Hospital Clínic-IDIBAPS-CIBERES, University of Barcelona, Barcelona, Spain. 4. Spartanburg Medical Research, Spartanburg, SC, USA. 5. Pulmonary Associates, Phoenix, AZ, USA. 6. Clinical Research of Rock Hill, Rock Hill, SC, USA. 7. New Horizons Clinical Research, Cincinnati, OH, USA. 8. University of North Carolina School of Medicine, Chapel Hill, NC, USA. 9. Pearl Therapeutics Inc., Morristown, NJ, USA. 10. Pearl Therapeutics Inc., Durham, NC, USA.
Abstract
BACKGROUND: 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. METHODS: 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 (FEV1 AUC0-12) on Day 7. RESULTS: 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 FEV1 AUC0-12 versus 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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. METHODS: 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 (FEV1 AUC0-12) on Day 7. RESULTS: 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 FEV1 AUC0-12 versus 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. CONCLUSIONS: 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.
Authors: Wilfried De Backer; Jan De Backer; Ilse Verlinden; Glenn Leemans; Cedric Van Holsbeke; Benjamin Mignot; Martin Jenkins; Dianne Griffis; Stefan Ivanov; Jane Fitzpatrick; Earl St Rose; Ubaldo J Martin; Colin Reisner Journal: Ther Adv Respir Dis Date: 2020 Jan-Dec Impact factor: 4.031