Original Research |

Efficacy and Safety of Glycopyrrolate/Formoterol MDI Formulated using Co-Suspension™ Delivery Technology in Patients with COPD OPEN ACCESS

Fernando J. Martinez, MD, MS, FCCP; Klaus F. Rabe, MD, PhD; Gary T. Ferguson, MD, FCCP; Leonardo M. Fabbri, MD, FCCP, FERS; Stephen Rennard, MD, FCCP; Gregory J. Feldman, MD; Sanjay Sethi, MD; Selwyn Spangenthal, MD; Gregory M. Gottschlich, MD, MS; Roberto Rodriguez-Roisin, MD, PhD, FCCP, FRCP, FERS; Samir Arora, MD; Thomas M. Siler, MD, FCCP; Shahid Siddiqui, MD, MHSA; Patrick Darken, PhD; Tracy Fischer, Pharm.D; Andrea Maes, PhD; Michael Golden, MS; Chad Orevillo, MPH; Colin Reisner, MD, FCCP, FAAAAI
Author and Funding Information

FUNDING/SUPPORT: PINNACLE-1 and PINNACLE-2 were supported by Pearl Therapeutics Inc., a member of the AstraZeneca Group.

CONFLICTS OF INTEREST: FJM reports personal fees from Adept, Afferent, Amgen, AstraZeneca, Axon, Axon Communication, Boehringer Ingelheim, Clarion, ConCert, Forest, Genentech, GlaxoSmithKline, Ikaria/Bellerophon, Informa, Janssen, Kadmon, Lucid, Methodist Hospital, Novartis, Nycomed/Takeda, Pearl Therapeutics Inc., Pfizer, Prime, Roche, Sunovion, Theravance, Unity Biotechnology, Veracyte, and WebMD. He has received non-financial support from Biogen/Stromedix, Boehringer Ingelheim, Centocor, and Gilead and grants from the National Institutes of Health. He has received personal fees for delivering CME programs for Academic CME, American Thoracic Society, Annenberg, California Society for Allergy and Immunology, CME Incite, Falco, Haymarket Communications, Integritas, InThought, Miller Medical, National Association for Continuing Education, Paradigm, Peer Voice, Potomac, UpToDate, and Western Society of Allergy and Immunology. He has received royalty fees from Informa. FJM has spoken on behalf of AstraZeneca and Nycomed/Takeda. He is currently a member of the GOLD Scientific Committee.

KFR reports grants from Boehringer Ingelheim, the German Federal Ministry of Education and Research (BMBF), and Novartis. He has received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Intermune, Novartis, and Takeda.

GTF reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Pearl Therapeutics Inc., Sunovian, and Theravance. He has received grants from Forest. He has received personal fees GlaxoSmithKline, Meda, Mylan, and Verona.

LMF reports grants, personal fees, and travel expenses reimbursement from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Laboratori Guidotti, Merck Sharp & Dohme, Menarini, Novartis, and Takeda. He has received personal fees and travel expenses reimbursement from Boston Scientific, Mundipharma and Pearl Therapeutics Inc. He has received personal fees from Bayer, Kyorin, and Zambon. LMF has received grants from Biofutura Italia, Dompè, Malesci, Pfizer, and Vree Health Italia.

SR reports grants from Almirall, AstraZeneca, Boehringer Ingelheim, Centocor, GlaxoSmithKline, NHLBI, Nebraska DHHS, Nycomed, Otsuka, and Pfizer. He has received personal fees from ABIM, Able Associates, Advantage Healthcare, Align2Action, Almirall, APT, ATS, AstraZeneca, Baxter, Boehringer-Ingelheim, Chiesi, CIPLA, ClearView Healthcare, Cleveland Clinic, CME Incite, Complete Medical Group, COPDFoundation, Cory Paeth, CSA, CSL, CTS Carmel, Daiichi Sankyo, Decision Resources, Dunn Group, Easton Associates, Elevation Pharma, FirstWord, Forest, Frankel Group, Gerson, Gilead, GlaxoSmithKline, Grifols, GroupH, Guidepoint Global, Haymarket, HealthStar, Huron Consulting, Incite, Inthought, IntraMed (Forest), Johnson & Johnson, LEK, McKinsey, Medical Knowledge, Medimmune, Methodist Health System, Navigant, NCI Consulting, Novartis, Nuvis, Pearl Therapeutics Inc., Penn Technology, Pfizer, PlanningShop, Prescott, Pro Ed Comm, ProiMed, PSL FirstWord, Pulmatrix, Quadrant, Qwessential, Regeneron, Saatchi and Saatchi, Schlesinger Associates, Strategic North, Synapse, Takeda, Theron, and WebMD. He is employed by AstraZeneca and also retains Professorship and a part-time appointment at the University of Nebraska Medical Center.

SSe reports grants from AstraZeneca, Dey, and Pearl Therapeutics Inc. He has received personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Cempra, CSL Behring, Forest, GlaxoSmithKline, Merck, Pearl Therapeutics Inc., Pulmonx, Reckitt Bencksier, Sunovion, and Theravance.

GG reports grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Pearl Therapeutics Inc., Sunovion, Theravance, Takeda, and Teva.

RR-R reports grants and personal fees from Almirall and Menarini. He has received personal fees from AstraZeneca, Boehringer Ingelheim, Ferrer, Mylan, Novartis, Pearl Therapeutics Inc., Takeda, and TEVA. He is member of the GOLD Board of Directors and of the Scientific Committee.

TS reports grants from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Forest Research, Novartis, Pearl Therapeutics Inc., Proterix, Sunovian, and Theravance. He has received personal fees from AstraZeneca, and Vapotherm.

SSi is an employee of AstraZeneca.

PD, TF, AM, MG, CO, and CR are employees of Pearl Therapeutics Inc.

GJF, SSp, and SA have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Clinical Trial Registration:ClinicalTrials.gov; No.: NCT01854645 and NCT01854658; URL: www.clinicaltrials.gov

aJoan and Sanford I Weill Department of Internal Medicine, Weill Cornell Medicine, New York, NY, USA

bLungenClinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany

cDepartment of Medicine, Christian-Albrechts University Kiel, Kiel, Germany

dPulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA

eDepartment of Medicine, University of Modena and Reggio Emilia, NOCSAE, Modena, Italy

fPulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, NE, USA

gClinical Discovery Unit, Early Clinical Development, AstraZeneca, Cambridge, UK

hS. Carolina Pharmaceutical Research, North Grove Medical Park, Spartanburg, SC, USA

iUniversity at Buffalo, SUNY, Buffalo, NY, USA

jAmerican Health Research, Inc., Charlotte, NC, USA

kNew Horizons Clinical Research, Cincinnati, OH, USA

lServei de Pneumologia, Institut Clinic Respiratori, Hospital Clínic, Barcelona, Spain; University of Barcelona, Barcelona, Spain

mColumbus Clinical Research, Columbus, OH, USA

nMidwest Chest Consultants, St Charles, MO, USA

oAstraZeneca, Gaithersburg, MD, USA (former employee of Pearl Therapeutics Inc.)

pPearl Therapeutics Inc., Morristown, NJ, USA

qPearl Therapeutics Inc., Durham, NC, USA

Correspondence to: Dr Fernando J. Martinez. Department of Internal Medicine, Weill Cornell Medicine, 525 East 68th St, New York, NY 10065.

Copyright 2016, . All Rights Reserved.

Chest. 2016. doi:10.1016/j.chest.2016.11.028
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Background  Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with chronic obstructive pulmonary disease (COPD) who continue to have symptoms despite treatment with a LAMA or LABA alone.

Objectives  The PINNACLE-1 (NCT01854645) and -2 (NCT01854658) trials investigated the efficacy and safety of a novel GFF MDI (glycopyrrolate [GP]/formoterol [FF] 18/9.6 μg metered dose inhaler [MDI]) formulated using Co-Suspension™ Delivery Technology, in patients with moderate-to-very severe COPD.

Methods  These two Phase III trials were 24-week, randomised, double-blind and placebo-controlled; and randomized 2103 and 1615 patients (40–80 years of age), respectively. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily; PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed.

Results  At Week 24, differences in change from baseline in morning pre-dose trough forced expiratory volume in 1 second for GFF MDI versus placebo MDI, GP MDI, and FF MDI were 150, 59, 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 to placebo and monocomponent MDIs, and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD.

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