Nicola A Hanania1, Donald P Tashkin2, Edward M Kerwin3, James F Donohue4, Michael Denenberg5, Denis E O'Donnell6, Dean Quinn7, Shahid Siddiqui8, Chad Orevillo9, Andrea Maes9, Colin Reisner10. 1. Baylor College of Medicine, Houston, TX, USA. Electronic address: hanania@bcm.edu. 2. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 3. Clinical Research Institute of Southern Oregon, Medford, OR, USA. 4. University of North Carolina School of Medicine, Chapel Hill, NC, USA. 5. Clinical Research of Rock Hill, Rock Hill, SC, USA. 6. Queen's University, Kingston, ON, Canada. 7. P3 Research Ltd., Newtown, Wellington, New Zealand. 8. AstraZeneca (Former Employee of Pearl Therapeutics Inc.), Gaithersburg, MD, USA. 9. Pearl Therapeutics Inc., Morristown, NJ, USA. 10. Pearl Therapeutics Inc., Morristown, NJ, USA; AstraZeneca, Morristown, NJ, USA.
Abstract
BACKGROUND: The long-term safety and efficacy of a novel Co-Suspension™ Delivery Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 μg fixed-dose combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: Subjects completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or open-label tiotropium 18 μg (once-daily) in PINNACLE-1 or -2 were randomly selected to continue treatment for 28 weeks. The target enrollment for PINNACLE-3 was 850 subjects. Safety and efficacy were evaluated over 52 weeks. RESULTS: Of 3274 subjects randomized to active treatment in PINNACLE-1 or -2, 892 entered PINNACLE-3. Incidences of adverse events, serious adverse events and major adverse cardiovascular events were similar across treatment groups with no unexpected safety findings. For change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1), treatment differences for GFF MDI versus GP MDI, FF MDI and open-label tiotropium over 52 weeks were 57, 65 and 25 mL, respectively (p ≤ 0.0117). Average daily rescue medication use was significantly reduced for GFF MDI versus GP MDI and open-label tiotropium (p ≤ 0.0002). Statistically significant improvements were observed with GFF MDI versus monocomponents in Self-Administered Computerized Transition Dyspnea Index focal score, and in St George's Respiratory Questionnaire total score versus GP MDI. CONCLUSIONS: Results confirmed the long-term safety and tolerability of GFF MDI 18/9.6 μg twice-daily in subjects with moderate-to-very severe COPD. Improvements in efficacy endpoints were also sustained over 52 weeks.
RCT Entities:
BACKGROUND: The long-term safety and efficacy of a novel Co-Suspension™ Delivery Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 μg fixed-dose combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: Subjects completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or open-label tiotropium 18 μg (once-daily) in PINNACLE-1 or -2 were randomly selected to continue treatment for 28 weeks. The target enrollment for PINNACLE-3 was 850 subjects. Safety and efficacy were evaluated over 52 weeks. RESULTS: Of 3274 subjects randomized to active treatment in PINNACLE-1 or -2, 892 entered PINNACLE-3. Incidences of adverse events, serious adverse events and major adverse cardiovascular events were similar across treatment groups with no unexpected safety findings. For change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1), treatment differences for GFF MDI versus GP MDI, FF MDI and open-label tiotropium over 52 weeks were 57, 65 and 25 mL, respectively (p ≤ 0.0117). Average daily rescue medication use was significantly reduced for GFF MDI versus GP MDI and open-label tiotropium (p ≤ 0.0002). Statistically significant improvements were observed with GFF MDI versus monocomponents in Self-Administered Computerized Transition Dyspnea Index focal score, and in St George's Respiratory Questionnaire total score versus GP MDI. CONCLUSIONS: Results confirmed the long-term safety and tolerability of GFF MDI 18/9.6 μg twice-daily in subjects with moderate-to-very severe COPD. Improvements in efficacy endpoints were also sustained over 52 weeks.
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: Fernando J Martinez; Brian J Lipworth; Klaus F Rabe; David J Collier; Gary T Ferguson; Sanjay Sethi; Gregory J Feldman; Gerald O'Brien; Martin Jenkins; Colin Reisner Journal: Respir Res Date: 2020-05-25
Authors: Wilfried De Backer; Jan De Backer; Wim Vos; Ilse Verlinden; Cedric Van Holsbeke; Johan Clukers; Bita Hajian; Shahid Siddiqui; Martin Jenkins; Colin Reisner; Ubaldo J Martin Journal: Int J Chron Obstruct Pulmon Dis Date: 2018-08-30
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