Fernando J Martinez1, Klaus F Rabe2, Gary T Ferguson3, Leonardo M Fabbri4, Stephen Rennard5, Gregory J Feldman6, Sanjay Sethi7, Selwyn Spangenthal8, Gregory M Gottschlich9, Roberto Rodriguez-Roisin10, Samir Arora11, Thomas M Siler12, Shahid Siddiqui13, Patrick Darken14, Tracy Fischer15, Andrea Maes14, Michael Golden16, Chad Orevillo17, Colin Reisner17. 1. Joan and Sanford Weill Department of Internal Medicine, Weill Cornell Medicine, New York, NY. Electronic address: fjm2003@med.cornell.edu. 2. LungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; and Department of Medicine, Christian-Albrechts University Kiel, Kiel, Germany. 3. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI. 4. Department of Medicine, University of Modena and Reggio Emilia, NOCSAE, Modena, Italy. 5. Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, NE. 6. Clinical Discovery Unit, Early Clinical Development, AstraZeneca, Cambridge, UK; and S. Carolina Pharmaceutical Research, North Grove Medical Park, Spartanburg, SC. 7. Department of Medicine, University at Buffalo, SUNY, Buffalo, NY. 8. Charlotte Lung and Health, American Health Research, Inc., Charlotte, NC. 9. New Horizons Clinical Research, Cincinnati, OH. 10. Servei de Pneumologia, Institut Clinic Respiratori, Hospital Clínic; and University of Barcelona, Barcelona, Spain. 11. Aventiv Research, Columbus, OH. 12. Midwest Chest Consultants, St. Charles, MO. 13. Respiratory, AstraZeneca, Gaithersburg, MD (former employee of Pearl Therapeutics, Inc.). 14. Biostatistics, Pearl Therapeutics, Inc., Morristown, NJ. 15. Regulatory Affairs, Pearl Therapeutics, Inc., Durham, NC. 16. Regulatory Affairs and Quality, Pearl Therapeutics, Inc., Durham, NC. 17. Clinical Development, Pearl Therapeutics, Inc., Morristown, NJ.
Abstract
BACKGROUND: Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-VerySevere COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD. METHODS: These two phase III trials took place over 24 weeks and were randomized, double blind, and placebocontrolled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed. RESULTS: At week 24, differences in change from baseline in the morning predose trough FEV1 for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms). CONCLUSIONS: We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov.
RCT Entities:
BACKGROUND: Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD. METHODS: These two phase III trials took place over 24 weeks and were randomized, double blind, and placebo controlled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed. RESULTS: At week 24, differences in change from baseline in the morning predose trough FEV1 for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms). CONCLUSIONS: We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov.
Authors: Colin Reisner; Gregory Gottschlich; Faisal Fakih; Andras Koser; James Krainson; Luis Delacruz; Samir Arora; Gregory Feldman; Krishna Pudi; Shahid Siddiqui; Chad Orevillo; Andrea Maes; Earl St Rose; Ubaldo Martin Journal: Respir Res Date: 2017-08-18
Authors: Lindsay G S Bengtson; Michael DePietro; Jeffrey McPheeters; Kathleen M Fox Journal: Ther Adv Respir Dis Date: 2018 Jan-Dec Impact factor: 4.031
Authors: Gary T Ferguson; Roberto Rodriguez-Roisin; Colin Reisner; Andrea Maes; Shahid Siddiqui; Ubaldo J Martin Journal: Int J Chron Obstruct Pulmon Dis Date: 2018-03-21