Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD (PINNACLE 2)

A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (24 Weeks), 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

This is a multicenter, randomized, double-blind, parallel group, chronic-dosing (24 weeks), placebo-controlled study to assess the efficacy and safety of Glycopyrrolate (GP and Formoterol Fumarate (FF) combination metered-dose inhaler (MDI) (GFF; PT003), GP MDI (PT001), and FF MDI (PT005) compared with Placebo MDI in subjects with moderate to very severe COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Placebo; Drug: FF MDI (PT005); Drug: GP MDI (PT001); Drug: GFF MDI (PT003)

• Study Type: Interventional
• Enrollment (Actual): 1615
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Pearl Investigative Site
    • Florence, Alabama, United States
      • Pearl Investigative Site
    • Jasper, Alabama, United States
      • Pearl Investigative Site
    • Mobile, Alabama, United States
      • Pearl Investigative Site
  • California
    • Fullerton, California, United States
      • Pearl Investigative Site
    • Gold River, California, United States
      • Pearl Investigative Site
    • Long Beach, California, United States
      • Pearl Investigative Site
    • Los Angeles, California, United States
      • Pearl Investigative Site
    • Mission Hills, California, United States
      • Pearl Investigative Site
    • Newport Beach, California, United States
      • Pearl Investigative Site
    • North Hollywood, California, United States
      • Pearl Investigative Site
    • Northridge, California, United States
      • Pearl Investigative Site
    • Rancho Mirage, California, United States
      • Pearl Investigative Site
    • Rialto, California, United States
      • Pearl Investigative Site
    • Rolling Hills Estates, California, United States
      • Pearl Investigative Site
    • San Diego, California, United States
      • Pearl Investigative Site
    • Santa Monica, California, United States
      • Pearl Investigative Site
    • Stockton, California, United States
      • Pearl Investigative Site
    • Torrance, California, United States
      • Pearl Investigative Site
    • Wildomar, California, United States
      • Pearl Investigative Site
  • Colorado
    • Centennial, Colorado, United States
      • Pearl Investigative Site
  • Florida
    • Boynton Beach, Florida, United States
      • Pearl Investigative Site
    • Clearwater, Florida, United States
      • Pearl Investigative Site
    • Hialeah, Florida, United States
      • Pearl Investigative Site
    • Jacksonville, Florida, United States
      • Pearl Investigative Site
    • Kissimmee, Florida, United States
      • Pearl Investigative Site
    • Melbourne, Florida, United States, u
      • Pearl Investigative Site
    • Miami, Florida, United States
      • Pearl Investigative Site
    • New Port Richey, Florida, United States
      • Pearl Investigative Site
    • Orlando, Florida, United States
      • Pearl Investigative Site
    • Ormond Beach, Florida, United States
      • Pearl Investigative Site
    • Port Orange, Florida, United States
      • Pearl Investigative Site
    • Sanford, Florida, United States
      • Pearl Investigative Site
    • Sebring, Florida, United States
      • Pearl Investigative Site
    • Tamarac, Florida, United States
      • Pearl Investigative Site
    • Winter Park, Florida, United States
      • Pearl Investigative Site
  • Georgia
    • Lawrenceville, Georgia, United States
      • Pearl Investigative Site
    • Norcross, Georgia, United States
      • Pearl Investigative Site
    • Smyrna, Georgia, United States
      • Pearl Investigative Site
  • Illinois
    • Elk Grove, Illinois, United States
      • Pearl Investigative Site
    • Normal, Illinois, United States
      • Pearl Investigative Site
    • Peoria, Illinois, United States
      • Pearl Investigative Site
  • Indiana
    • Evansville, Indiana, United States
      • Pearl Investigative Site
    • Franklin, Indiana, United States
      • Pearl Investigative Site
    • Lafayette, Indiana, United States
      • Pearl Investigative Site
    • South Bend, Indiana, United States
      • Pearl Investigative Site
  • Iowa
    • Council Bluffs, Iowa, United States
      • Pearl Investigative Site
  • Kentucky
    • Hazard, Kentucky, United States
      • Pearl Investigative Site
    • Louisville, Kentucky, United States
      • Pearl Investigative Site
    • Paducah, Kentucky, United States
      • Pearl Investigative Site
  • Louisiana
    • Lake Charles, Louisiana, United States
      • Pearl Investigative Site
  • Maryland
    • Baltimore, Maryland, United States
      • Pearl Investigative Siteq
    • Columbia, Maryland, United States
      • Pearl Investigative Site
  • Massachusetts
    • Haverhill, Massachusetts, United States
      • Pearl Investigative Site
    • North Dartmouth, Massachusetts, United States
      • Pearl Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States
      • Pearl Investigative Site
  • Minnesota
    • Fridley, Minnesota, United States
      • Pearl Investigative Site
    • Minneapolis, Minnesota, United States
      • Pearl Investigative Site
    • Rochester, Minnesota, United States
      • Pearl Investigative Site
  • Missouri
    • St Charles, Missouri, United States
      • Pearl Investigative Site
    • St Louis, Missouri, United States
      • Pearl Investigative Site
    • St. Louis, Missouri, United States
      • Pearl Investigative Site
  • Nebraska
    • Fremont, Nebraska, United States
      • Pearl Investigative Site
    • Omaha, Nebraska, United States
      • Pearl Investigative Site
  • Nevada
    • Henderson, Nevada, United States
      • Pearl Investigative Site
  • New Hampshire
    • Newington, New Hampshire, United States
      • Pearl Investigative Site
  • New Jersey
    • Cedar Knolls, New Jersey, United States
      • Pearl Investigative Site
    • Marlton, New Jersey, United States
      • Pearl Investigative Site
  • New York
    • Buffalo, New York, United States
      • Pearl Investigative Site
    • New York, New York, United States
      • Pearl Investigative Site
    • Rochester, New York, United States
      • Pearl Investigative Site
  • North Carolina
    • Boone, North Carolina, United States
      • Pearl Investigative Site
    • Charlotte, North Carolina, United States
      • Pearl Investigative Site
    • Hendersonville, North Carolina, United States
      • Pearl Investigative Site
    • Raleigh, North Carolina, United States
      • Pearl Investigative Site
    • Winston-Salem, North Carolina, United States
      • Pearl Investigative Site
  • Ohio
    • Akron, Ohio, United States
      • Pearl Investigative Site
    • Canton, Ohio, United States
      • Pearl Investigative Site
    • Cincinnati, Ohio, United States
      • Pearl Investigative Site
    • Columbus, Ohio, United States
      • Pearl Investigative Site
    • Willoughby, Ohio, United States
      • Pearl Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Pearl Investigative Site
    • Tulsa, Oklahoma, United States
      • Pearl Investigative Site
  • Oregon
    • Portland, Oregon, United States
      • Pearl Investigative Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • Pearl Investigative Site
    • Phoenixville, Pennsylvania, United States
      • Pearl Investigative Site
    • Pittsburgh, Pennsylvania, United States
      • Pearl Investigative Site
  • South Carolina
    • Anderson, South Carolina, United States
      • Pearl Investigative Site
    • Charleston, South Carolina, United States
      • Pearl Investigative Site
    • Easley, South Carolina, United States
      • Pearl Investigative Site
    • Fort Mill, South Carolina, United States
      • Pearl Investigative Site
    • Gaffney, South Carolina, United States
      • Pearl Investigative Site
    • Greenville, South Carolina, United States
      • Pearl Investigative Site
    • Rock Hill, South Carolina, United States
      • Pearl Investigative Site
    • Seneca, South Carolina, United States
      • Pearl Investigative Site
    • Spartanburg, South Carolina, United States
      • Pearl Investigative Site
  • Tennessee
    • Nashville, Tennessee, United States
      • Pearl Investigative Site
  • Texas
    • Arlington, Texas, United States
      • Pearl Investigative Site
    • Beaumont, Texas, United States
      • Pearl Investigative Site
    • Boerne, Texas, United States
      • Pearl Investigative Site
    • Corsicana, Texas, United States
      • Pearl Investigative Site
    • Dallas, Texas, United States
      • Pearl Investigative Site
    • Fort Worth, Texas, United States
      • Pearl Investigative Site
    • Houston, Texas, United States
      • Pearl Investigative Site
    • San Antonio, Texas, United States
      • Pearl Investigative Site
    • Tomball, Texas, United States
      • Pearl Investigative Site
    • Waco, Texas, United States
      • Pearl Investigative Site
  • Virginia
    • Midlothian, Virginia, United States
      • Pearl Investigative Site
    • Newport News, Virginia, United States
      • Pearl Investigative Site
    • Richmond, Virginia, United States
      • Pearl Investigative Site
    • Ricmond, Virginia, United States
      • Pearl Investigative Site
  • Washington
    • Spokane, Washington, United States
      • Pearl Investigative Site
    • Tacoma, Washington, United States
      • Pearl Investigative Site
  • West Virginia
    • Bridgeport, West Virginia, 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.
• Subjects with FEV1/FVC ratio of <0.70 and FEV1 <80% predicted normal and ≥750 mL if FEV1 <30% of predicted normal value.
• 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 NYHA Class III/IV)
• Clinically significant abnormal 12-lead ECG
• Abnormal liver function tests defined as AST, 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
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FF MDI (PT005); FF MDI administered as two puffs BID	Drug: FF MDI (PT005); FF MDI administered as two puffs BID; Other Names: formoterol fumarate metered dose inhaler (FF MDI)
EXPERIMENTAL: GP MDI (PT001); GP MDI administered as two puffs BID	Drug: GP MDI (PT001); GP MDI administered as two puffs BID; Other Names: glycopyrrolate metered dose inhaler (GP MDI)
EXPERIMENTAL: GFF MDI (PT003); GFF MDI administered as two puffs BID	Drug: GFF MDI (PT003); GFF MDI administered as two puffs BID; Other Names: glycopyrrolate/formoterol fumarate metered-dose inhaler; (GFF MDI)
PLACEBO_COMPARATOR: Placebo MDI; Inhaled placebo administered as two puffs BID	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Morning Pre-dose Trough FEV1	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) at Week 24.	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 model-based 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.	Over 24 weeks
Peak FEV1	Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24	At week 24
St. George Respiratory Questionnaire (SGRQ) Score	Change from baseline in the SGRQ total score at Week 24. 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.	24 weeks
Rescue Ventolin HFA Use	Change from baseline in average daily rescue Ventolin HFA use over 24 weeks	24 weeks
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	Day 1

Collaborators and Investigators

• Sponsor: 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

• PT003007-02 Protocol Amendment-FINAL-Redacted.pdf

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): March 1, 2015

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: May 14, 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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: PT003007-00