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

A Randomized, Double Blind, Chronic Dosing, Placebo-Controlled, Parallel Group, Multi Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo and Spiriva® Handihaler® (Tiotropium Bromide 18 µg Open-Label) as an Active Control

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: GFF MDI; Drug: GP MDI; Drug: FF MDI; Drug: Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®); Drug: Placebo MDI

• Study Type: Interventional
• Enrollment (Actual): 2103
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia
      • Pearl Investigative Site
    • Westmead, New South Wales, Australia
      • Pearl Investigative Site
  • Queensland
    • Brisbane, Queensland, Australia
      • Pearl Investigative Site
    • Cairns, Queensland, Australia
      • Pearl Investigative Site
    • Wooloongabba, Queensland, Australia
      • Pearl Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Pearl Investigative Site
    • Daw Park, South Australia, Australia
      • Pearl Investigative Site
    • Toorak Gardens, South Australia, Australia
      • Pearl Investigative Site
  • Victoria
    • Box Hill, Victoria, Australia
      • Pearl Investigative Site
    • Heidelberg, Victoria, Australia
      • Pearl Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Pearl Investigative Site
    • Perth, Western Australia, Australia
      • Pearl Investigative Site
• New Zealand
  • Tauranga, New Zealand
    • Pearl Investigative Site
  • Aukland
    • Otahuhu, Aukland, New Zealand
      • Pearl Investigative Site
  • Dunedin
    • Caversham, Dunedin, New Zealand
      • Pearl Investigative Site
  • East Aukland
    • Greenlane, East Aukland, New Zealand
      • Pearl Investigative Site
  • Waikato
    • Hamilton, Waikato, New Zealand
      • Pearl Investigative Site
  • Wellington
    • Newtown, Wellington, New Zealand
      • Pearl Investigative Site
• United States
  • Alabama
    • Andalusia, Alabama, United States
      • Pearl Investigative Site
    • Anniston, Alabama, United States
      • Pearl Investigative Site
    • Athens, Alabama, United States
      • Pearl Investigative Site
    • Birmingham, Alabama, United States
      • Pearl Investigative Site
  • Arizona
    • Mesa, Arizona, United States
      • Pearl Investigative Site
    • Phoenix, Arizona, United States
      • Pearl Investigative Site
    • Scottsdale, Arizona, United States
      • Pearl Investigative Site
    • Tucson, Arizona, United States
      • Pearl Investigative Site
  • California
    • Anaheim, California, United States
      • Pearl Investigative Site
    • Carlsbad, California, United States
      • Pearl Investigative Site
    • Lakewood, California, United States
      • Pearl Investigative Site
    • Los Angeles, California, United States
      • Pearl Investigative Site
    • Pasadena, California, United States
      • Pearl Investigative Site
    • Pasedena, California, United States
      • Pearl Investigative Site
    • Poway, California, United States
      • Pearl Investigative Site
    • Sacramento, California, United States
      • Pearl Investigative Site
    • San Diego, California, United States
      • Pearl Investigative Site
    • Tustin, California, United States
      • Pearl Investigative Site
    • Vista, California, United States
      • Pearl Investigative Site
  • Colorado
    • Colorado Springs, Colorado, United States
      • Pearl Investigative Site
    • Denver, Colorado, United States
      • Pearl Investigative Site
    • Fort Collins, Colorado, United States
      • Pearl Investigative Site
    • Wheat Ridge, Colorado, United States
      • Pearl Investigative Site
  • Connecticut
    • Danbury, Connecticut, United States
      • Pearl Investigative Site
    • Waterbury, Connecticut, United States
      • Pearl Investigative Site
  • Florida
    • Brandon, Florida, United States
      • Pearl Investigative Site
    • Clearwater, Florida, United States
      • Pearl Investigative Site
    • Lehigh Acres, Florida, United States
      • Pearl Investigative Site
    • Miami, Florida, United States
      • Pearl Investigative Site
    • Ormond Beach, Florida, United States
      • Pearl Investigative Site
    • Panama City, Florida, United States
      • Pearl Investigative Site
    • Pensacola, Florida, United States
      • Pearl Investigative Site
    • St. Petersburg, Florida, United States
      • Pearl Investigative Site
    • Tampa, Florida, United States
      • Pearl Investigative Site
    • Winter Park, Florida, United States
      • Pearl Investigative Site
  • Georgia
    • Atlanta, Georgia, United States
      • Pearl Investigative Site
    • Austell, Georgia, United States
      • Pearl Investigative Site
    • Columbus, Georgia, United States
      • Pearl Investigative Site
    • Duluth, Georgia, United States
      • Pearl Investigative Site
    • Gainesville, Georgia, United States
      • Pearl Investigative Site
  • Idaho
    • Coeur d'Alene, Idaho, United States
      • Pearl Investigative Site
  • Illinois
    • Champaign, Illinois, United States
      • Pearl Investigative Site
    • Evanston, Illinois, United States
      • Pearl Investigative Site
    • Peoria, Illinois, United States
      • Pearl Investigative Site
    • River Forest, Illinois, United States
      • Pearl Investigative Site
  • Indiana
    • Anderson, Indiana, United States
      • Pearl Investigative Site
    • Avon, Indiana, United States
      • Pearl Investigative Site
    • Elwood, Indiana, United States
      • Pearl Investigative Site
    • Evansville, Indiana, United States
      • Pearl Investigative Site
  • Iowa
    • Iowa City, Iowa, United States
      • Pearl Investigative Site
  • Kansas
    • Topeka, Kansas, United States
      • Pearl Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States
      • Pearl Investigative Site
  • Louisiana
    • Lafayette, Louisiana, United States
      • Pearl Investigative Site
    • Sunset, Louisiana, United States
      • Pearl Investigative Site
  • Maryland
    • Baltimore, Maryland, United States
      • Pearl Investigative Site
    • Hollywood, Maryland, United States
      • Pearl Investigative Site
  • Michigan
    • Livonia, Michigan, United States
      • Pearl Investigative Site
    • Southfield, Michigan, United States
      • Pearl Investigative Site
  • Minnesota
    • Edina, Minnesota, United States
      • Pearl Investigative Site
    • Fridley, Minnesota, United States
      • Pearl Investigative Site
    • Minneapolis, Minnesota, United States
      • Pearl Investigative Site
    • Woodbury, Minnesota, United States
      • Pearl Investigative Site
  • Missouri
    • Springfield, Missouri, United States
      • Pearl Investigative Site
    • St Louis, Missouri, United States
      • Pearl Investigative Site
    • St. Charles, Missouri, United States
      • Pearl Investigative Site
  • Montana
    • Missoula, Montana, United States
      • Pearl Investigative Site
  • Nebraska
    • Bellevue, Nebraska, United States
      • Pearl Investigative Site
    • Omaha, Nebraska, United States
      • Pearl Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Pearl Investigative Site
  • New Jersey
    • Ocean, New Jersey, United States
      • Pearl Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Pearl Investigative Site
  • New York
    • Corning, New York, United States
      • Pearl Investigative Site
  • North Carolina
    • Burlington, North Carolina, United States
      • Pearl Investigative Site
    • Charlotte, North Carolina, United States
      • Pearl Investigative Site
    • Greensboro, North Carolina, United States
      • Pearl Investigative Site
    • Huntersville, North Carolina, United States
      • Pearl Investigative Site
    • Raleigh, North Carolina, United States
      • Pearl Investigative Site
    • Wilmington, North Carolina, United States
      • Pearl Investigative Site
    • Winston-Salem, North Carolina, United States
      • Pearl Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Pearl Investigative Site
    • Columbus, Ohio, United States
      • Pearl Investigative Site
    • Dayton, Ohio, United States
      • Pearl Investigative Site
    • Dublin, Ohio, United States
      • Pearl Investigative Site
    • Oregon, Ohio, United States
      • Pearl Investigative Site
  • Oregon
    • Bend, Oregon, United States
      • Pearl Investigative Site
    • Medford, Oregon, United States
      • Pearl Investigative Site
    • Portland, Oregon, United States
      • Pearl Investigative Site
  • Pennsylvania
    • Monroeville, Pennsylvania, United States
      • Pearl Investigative Site
    • Philadelphia, Pennsylvania, United States
      • Pearl Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Pearl Investigative Site
    • Easley, South Carolina, United States
      • Pearl Investigative Site
    • Gaffney, South Carolina, United States
      • Pearl Investigative Site
    • Greenville, South Carolina, United States
      • Pearl Investigative Site
    • Mt. Pleasant, South Carolina, United States
      • Pearl Investigative Site
    • Murrells Inlet, South Carolina, United States
      • Pearl Investigative Site
    • Myrtle Beach, South Carolina, United States
      • Pearl Investigative Site
    • Rock Hill, South Carolina, United States
      • Pearl Investigative Site
    • Spartanburg, South Carolina, United States
      • Pearl Investigative Site
    • Union, South Carolina, United States
      • Pearl Investigative Site
  • South Dakota
    • Rapid City, South Dakota, United States
      • Pearl Investigative Site
  • Tennessee
    • Bristol, Tennessee, United States
      • Pearl Investigative Site
    • Johnson City, Tennessee, United States
      • Pearl Investigative Site
    • Kingsport, Tennessee, United States
      • Pearl Investigative Site
    • Tullahoma, Tennessee, United States
      • Pearl Investigative Site
  • Texas
    • Austin, Texas, United States
      • Pearl Investigative Site
    • El Paso, Texas, United States
      • Pearl Investigative Site
    • Fort Worth, Texas, United States
      • Pearl Investigative Site
    • Houston, Texas, United States
      • Pearl Investigative Site
    • Huntsville, Texas, United States
      • Pearl Investigative Site
    • Longview, Texas, United States
      • Pearl Investigative Site
    • Lufkin, Texas, United States
      • Pearl Investigative Site
    • New Braunfels, Texas, United States
      • Pearl Investigative Site
    • San Antonio, Texas, United States
      • Pearl Investigative Site
  • Utah
    • Midvale, Utah, United States
      • Pearl Investigative Site
    • Salt Lake City, Utah, United States
      • Pearl Investigative Site
  • Vermont
    • South Burlington, Vermont, United States
      • Pearl Investigative Site
  • Virginia
    • Abingdon, Virginia, United States
      • Pearl Investigative Site
    • Richmond, Virginia, United States
      • Pearl Investigative Site
  • Washington
    • Spokane, Washington, United States
      • Pearl Investigative Site
    • Tacoma, Washington, United States
      • Pearl Investigative Site
  • West Virginia
    • Morgantown, West Virginia, United States
      • Pearl Investigative Site
  • Wisconsin
    • West Allis, Wisconsin, United States
      • Pearl Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GFF MDI; Glycopyrronium Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) (PT003)	Drug: GFF MDI; GFF MDI administered as two puffs Bis in Di.e. Twice Daily (BID)
Experimental: GP MDI; Glycopyrronium (GP) MDI (PT001)	Drug: GP MDI; GP MDI administered as two puffs BID
Experimental: FF MDI; Formoterol Fumarate (FF) MDI (PT005)	Drug: FF MDI; FF MDI administered as two puffs BID
Active Comparator: Open-label tiotropium bromide inhalation powder; Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)	Drug: Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®); Taken as 1 capsule daily containing 18 µg of open-label tiotropium via the Handihaler dry powder inhaler (DPI)
Placebo Comparator: Placebo; Placebo MDI	Drug: Placebo MDI; Inhaled placebo administered as two puffs BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) over 24 weeks. FEV1 was assessed at multiple time points post-baseline,and a modelbased average of all visits starting from Week 2 through week 24 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average FEV1 post-baseline.	Baseline and Weeks 2 to 24
St. George's Respiratory Questionnaire (SGRQ) Score	Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.	Baseline and at Week 24
Rescue Ventolin Hydrofluoroalkane (HFA) Use	Change from baseline in average daily rescue Ventolin HFA use	Baseline and at Week 24
Onset of Action as Assessed by FEV1	Defined as the first time-point using the 5- and 15-minute post dose measurements where the difference in FEV1 from Placebo was statistically significant	Assessed for 5- and 15-minute post dose on Day 1
Peak Change From Baseline in FEV1 Within 2 Hours Post-dose	Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 2 hours post-dose	Baseline and at Week 24

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Colin Reisner, MD, Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Helpful Links

• PT003006-02 Protocol and Amendment-FINAL-Redacted

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: May 13, 2013
• First Posted (Estimate): May 15, 2013

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: PT003006-00