Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD); (PINNACLE 1)

NCT01854645 | Completed Phase 3 Results DMC

• 1 other identifier: PT003006-00
• Study Type: interventional
• Target: 2,103
• Locations: 3 countries
• Sites: 139

Brief Summary

The overall objective of this study is to assess the efficacy and safety of treatment with PT003 (GFF MDI), PT005 (FF MDI), PT001 (GP MDI), and open-label tiotropium bromide inhalation powder compared with each other and Placebo MDI over 24 weeks in subjects with moderate to very severe COPD.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24

  Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) at Week 24

  Baseline and at Week 24

Secondary Outcomes (5)

• Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks

  Baseline and Weeks 2 to 24

• St. George's Respiratory Questionnaire (SGRQ) Score

  Baseline and at Week 24

• Rescue Ventolin Hydrofluoroalkane (HFA) Use

  Baseline and at Week 24

• Onset of Action as Assessed by FEV1

  Assessed for 5- and 15-minute post dose on Day 1

• Peak Change From Baseline in FEV1 Within 2 Hours Post-dose

  Baseline and at Week 24

Study Arms (5)

GFF MDI

EXPERIMENTAL

Glycopyrronium Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) (PT003)

Drug: GFF MDI

GP MDI

EXPERIMENTAL

Glycopyrronium (GP) MDI (PT001)

Drug: GP MDI

FF MDI

EXPERIMENTAL

Formoterol Fumarate (FF) MDI (PT005)

Drug: FF MDI

Open-label tiotropium bromide inhalation powder

ACTIVE COMPARATOR

Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)

Drug: Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)

Placebo

PLACEBO COMPARATOR

Placebo MDI

Drug: Placebo MDI

Interventions

GFF MDI DRUG

GFF MDI administered as two puffs Bis in Di.e. Twice Daily (BID)

GFF MDI

GP MDI DRUG

GP MDI administered as two puffs BID

GP MDI

FF MDI DRUG

FF MDI administered as two puffs BID

FF MDI

Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®) DRUG

Taken as 1 capsule daily containing 18 µg of open-label tiotropium via the Handihaler dry powder inhaler (DPI)

Open-label tiotropium bromide inhalation powder

Placebo MDI DRUG

Inhaled placebo administered as two puffs BID

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects at least 40 years of age and no older than 80 at Visit 1.
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.
• Average f the -60 and the -30 min pre-dose FEV1 assessments must be \< 80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations.
• Subjects willing and, in the opinion of the investigator, able to adjust current COPD therapy as required by the protocol

You may not qualify if:

• Significant diseases other than COPD, i.e. disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study
• Current diagnosis of asthma or alpha-1 antitrypsin deficiency
• Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea
• Hospitalized due to poorly controlled COPD within 3 months prior to screening or during the Screening Period
• Poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to screening or during the Screening Period
• Lower respiratory tract infections that required antibiotics within 6 weeks prior to screening or during the Screening Period
• Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of enrollment.
• Recent history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft within the past three months
• Congestive heart failure (CHF) New York Heart Association (NYHA) Class III/IV)
• Clinically significant abnormal 12-lead ECG
• Abnormal liver function tests defined as aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin ≥ 1.5 times upper limit of normal at Visit 1 and on repeat testing
• Cancer not in complete remission for at least five years
• History of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, lactose/milk protein or any component of the MDI

Sponsors & Collaborators

• Pearl Therapeutics, Inc.: lead

Study Sites (139)

Pearl Investigative Site

Andalusia, Alabama, United States

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Anniston, Alabama, United States

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Athens, Alabama, United States

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Birmingham, Alabama, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Carlsbad, California, United States

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Lakewood, California, United States

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Los Angeles, California, United States

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Pasadena, California, United States

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Poway, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Tustin, California, United States

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Vista, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Fort Collins, Colorado, United States

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Wheat Ridge, Colorado, United States

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Danbury, Connecticut, United States

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Waterbury, Connecticut, United States

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Brandon, Florida, United States

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Clearwater, Florida, United States

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Lehigh Acres, Florida, United States

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Miami, Florida, United States

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Ormond Beach, Florida, United States

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Panama City, Florida, United States

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Pensacola, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Atlanta, Georgia, United States

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Austell, Georgia, United States

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Columbus, Georgia, United States

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Duluth, Georgia, United States

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Gainesville, Georgia, United States

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Coeur d'Alene, Idaho, United States

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Champaign, Illinois, United States

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Evanston, Illinois, United States

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Peoria, Illinois, United States

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River Forest, Illinois, United States

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Anderson, Indiana, United States

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Avon, Indiana, United States

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Elwood, Indiana, United States

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Evansville, Indiana, United States

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Iowa City, Iowa, United States

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Topeka, Kansas, United States

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Louisville, Kentucky, United States

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Lafayette, Louisiana, United States

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Sunset, Louisiana, United States

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Baltimore, Maryland, United States

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Hollywood, Maryland, United States

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Livonia, Michigan, United States

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Southfield, Michigan, United States

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Edina, Minnesota, United States

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Fridley, Minnesota, United States

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Minneapolis, Minnesota, United States

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Woodbury, Minnesota, United States

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Saint Charles, Missouri, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Bellevue, Nebraska, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Ocean City, New Jersey, United States

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Albuquerque, New Mexico, United States

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Corning, New York, United States

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Burlington, North Carolina, United States

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Charlotte, North Carolina, United States

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Greensboro, North Carolina, United States

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Huntersville, North Carolina, United States

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Raleigh, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Dayton, Ohio, United States

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Dublin, Ohio, United States

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Oregon, Ohio, United States

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Bend, Oregon, United States

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Medford, Oregon, United States

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Portland, Oregon, United States

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Monroeville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Easley, South Carolina, United States

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Gaffney, South Carolina, United States

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Greenville, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Murrells Inlet, South Carolina, United States

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Myrtle Beach, South Carolina, United States

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Rock Hill, South Carolina, United States

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Spartanburg, South Carolina, United States

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Union, South Carolina, United States

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Rapid City, South Dakota, United States

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Bristol, Tennessee, United States

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Johnson City, Tennessee, United States

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Kingsport, Tennessee, United States

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Tullahoma, Tennessee, United States

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Austin, Texas, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Huntsville, Texas, United States

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Longview, Texas, United States

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Lufkin, Texas, United States

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New Braunfels, Texas, United States

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San Antonio, Texas, United States

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Midvale, Utah, United States

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Salt Lake City, Utah, United States

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South Burlington, Vermont, United States

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Abingdon, Virginia, United States

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Richmond, Virginia, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Morgantown, West Virginia, United States

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West Allis, Wisconsin, United States

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New Lambton, New South Wales, Australia

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Westmead, New South Wales, Australia

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Brisbane, Queensland, Australia

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Cairns, Queensland, Australia

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Wooloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Daw Park, South Australia, Australia

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Toorak Gardens, South Australia, Australia

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Box Hill, Victoria, Australia

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Heidelberg, Victoria, Australia

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Nedlands, Western Australia, Australia

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Perth, Western Australia, Australia

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Otahuhu, Aukland, New Zealand

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Caversham, Dunedin, New Zealand

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Greenlane, East Aukland, New Zealand

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Hamilton, Waikato Region, New Zealand

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Newtown, Wellington Region, New Zealand

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Tauranga, New Zealand

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Related Publications (4)

• Singh D, Hurst JR, Martinez FJ, Rabe KF, Bafadhel M, Jenkins M, Salazar D, Dorinsky P, Darken P. Predictive modeling of COPD exacerbation rates using baseline risk factors. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221107314. doi: 10.1177/17534666221107314.

  PMID: 35815359 DERIVED

• Martinez FJ, Lipworth BJ, Rabe KF, Collier DJ, Ferguson GT, Sethi S, Feldman GJ, O'Brien G, Jenkins M, Reisner C. Benefits of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in improving lung function and reducing exacerbations in patients with moderate-to-very severe COPD: a pooled analysis of the PINNACLE studies. Respir Res. 2020 May 25;21(1):128. doi: 10.1186/s12931-020-01388-y.

  PMID: 32450869 DERIVED

• Martinez FJ, Rabe KF, Lipworth BJ, Arora S, Jenkins M, Martin UJ, Reisner C. Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Lung Function versus Monotherapies in GOLD Category A Patients with COPD: Pooled Data from the Phase III PINNACLE Studies. Int J Chron Obstruct Pulmon Dis. 2020 Jan 9;15:99-106. doi: 10.2147/COPD.S229794. eCollection 2020.

  PMID: 32021148 DERIVED

• Martinez FJ, Fabbri LM, Ferguson GT, Orevillo C, Darken P, Martin UJ, Reisner C. Baseline Symptom Score Impact on Benefits of Glycopyrrolate/Formoterol Metered Dose Inhaler in COPD. Chest. 2017 Dec;152(6):1169-1178. doi: 10.1016/j.chest.2017.07.007. Epub 2017 Jul 16.

  PMID: 28720336 DERIVED

Related Links

• PT003006-02 Protocol and Amendment-FINAL-Redacted

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Colin Reisner, MD, FCCP, FAAAAI
• Organization: Pearl Therapeutics, Inc

creisner@pearltherapeutics.com

973-975-0320

Study Officials

• Colin Reisner, MD

  Pearl Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2013
• First Posted: May 15, 2013
• Study Start: May 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 28, 2017
• Results First Posted: March 28, 2017

Record last verified: 2017-02

Locations

AU (12); NZ (6); US (121)