Clinical trial NCT01854645: Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD); (PINNACLE 1)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-15
Enrollment: 2103
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24
timeFrame: Baseline and at Week 24
Secondary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks
timeFrame: Baseline and Weeks 2 to 24
measure: St. George's Respiratory Questionnaire (SGRQ) Score
timeFrame: Baseline and at Week 24
measure: Rescue Ventolin Hydrofluoroalkane (HFA) Use
timeFrame: Baseline and at Week 24
measure: Onset of Action as Assessed by FEV1
timeFrame: Assessed for 5- and 15-minute post dose on Day 1
measure: Peak Change From Baseline in FEV1 Within 2 Hours Post-dose
timeFrame: Baseline and at Week 24
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Anniston
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Athens
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Birmingham
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Mesa
country: United States
facility: Pearl Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Pearl Investigative Site
state: Arizona
city: Scottsdale
country: United States
facility: Pearl Investigative Site
state: Arizona
city: Tucson
country: United States
facility: Pearl Investigative Site
state: Arizona
city: Anaheim
country: United States
facility: Pearl Investigative Site
state: California
city: Carlsbad
country: United States
facility: Pearl Investigative Site
state: California
city: Lakewood
country: United States
facility: Pearl Investigative Site
state: California
city: Los Angeles
country: United States
facility: Pearl Investigative Site
state: California
city: Pasadena
country: United States
facility: Pearl Investigative Site
state: California
city: Pasedena
country: United States
facility: Pearl Investigative Site
state: California
city: Poway
country: United States
facility: Pearl Investigative Site
state: California
city: Sacramento
country: United States
facility: Pearl Investigative Site
state: California
city: San Diego
country: United States
facility: Pearl Investigative Site
state: California
city: Tustin
country: United States
facility: Pearl Investigative Site
state: California
city: Vista
country: United States
facility: Pearl Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Pearl Investigative Site
state: Colorado
city: Denver
country: United States
facility: Pearl Investigative Site
state: Colorado
city: Fort Collins
country: United States
facility: Pearl Investigative Site
state: Colorado
city: Wheat Ridge
country: United States
facility: Pearl Investigative Site
state: Colorado
city: Danbury
country: United States
facility: Pearl Investigative Site
state: Connecticut
city: Waterbury
country: United States
facility: Pearl Investigative Site
state: Connecticut
city: Brandon
country: United States
facility: Pearl Investigative Site
state: Florida
city: Clearwater
country: United States
facility: Pearl Investigative Site
state: Florida
city: Lehigh Acres
country: United States
facility: Pearl Investigative Site
state: Florida
city: Miami
country: United States
facility: Pearl Investigative Site
state: Florida
city: Ormond Beach
country: United States
facility: Pearl Investigative Site
state: Florida
city: Panama City
country: United States
facility: Pearl Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Pearl Investigative Site
state: Florida
city: St. Petersburg
country: United States
facility: Pearl Investigative Site
state: Florida
city: Tampa
country: United States
facility: Pearl Investigative Site
state: Florida
city: Winter Park
country: United States
facility: Pearl Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Austell
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Columbus
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Duluth
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Gainesville
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Coeur d'Alene
country: United States
facility: Pearl Investigative Site
state: Idaho
city: Champaign
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Evanston
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Peoria
country: United States
facility: Pearl Investigative Site
state: Illinois
city: River Forest
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Anderson
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Avon
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Elwood
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Evansville
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Iowa City
country: United States
facility: Pearl Investigative Site
state: Iowa
city: Topeka
country: United States
facility: Pearl Investigative Site
state: Kansas
city: Louisville
country: United States
facility: Pearl Investigative Site
state: Kentucky
city: Lafayette
country: United States
facility: Pearl Investigative Site
state: Louisiana
city: Sunset
country: United States
facility: Pearl Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Pearl Investigative Site
state: Maryland
city: Hollywood
country: United States
facility: Pearl Investigative Site
state: Maryland
city: Livonia
country: United States
facility: Pearl Investigative Site
state: Michigan
city: Southfield
country: United States
facility: Pearl Investigative Site
state: Michigan
city: Edina
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Fridley
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Minneapolis
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Woodbury
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Springfield
country: United States
facility: Pearl Investigative Site
state: Missouri
city: St Louis
country: United States
facility: Pearl Investigative Site
state: Missouri
city: St. Charles
country: United States
facility: Pearl Investigative Site
state: Missouri
city: Missoula
country: United States
facility: Pearl Investigative Site
state: Montana
city: Bellevue
country: United States
facility: Pearl Investigative Site
state: Nebraska
city: Omaha
country: United States
facility: Pearl Investigative Site
state: Nebraska
city: Las Vegas
country: United States
facility: Pearl Investigative Site
state: Nevada
city: Ocean
country: United States
facility: Pearl Investigative Site
state: New Jersey
city: Albuquerque
country: United States
facility: Pearl Investigative Site
state: New Mexico
city: Corning
country: United States
facility: Pearl Investigative Site
state: New York
city: Burlington
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Greensboro
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Huntersville
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Raleigh
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Wilmington
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Dayton
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Dublin
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Oregon
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Bend
country: United States
facility: Pearl Investigative Site
state: Oregon
city: Medford
country: United States
facility: Pearl Investigative Site
state: Oregon
city: Portland
country: United States
facility: Pearl Investigative Site
state: Oregon
city: Monroeville
country: United States
facility: Pearl Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pearl Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Easley
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Gaffney
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Greenville
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Mt. Pleasant
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Murrells Inlet
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Myrtle Beach
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Rock Hill
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Spartanburg
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Union
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Rapid City
country: United States
facility: Pearl Investigative Site
state: South Dakota
city: Bristol
country: United States
facility: Pearl Investigative Site
state: Tennessee
city: Johnson City
country: United States
facility: Pearl Investigative Site
state: Tennessee
city: Kingsport
country: United States
facility: Pearl Investigative Site
state: Tennessee
city: Tullahoma
country: United States
facility: Pearl Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Pearl Investigative Site
state: Texas
city: El Paso
country: United States
facility: Pearl Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Pearl Investigative Site
state: Texas
city: Houston
country: United States
facility: Pearl Investigative Site
state: Texas
city: Huntsville
country: United States
facility: Pearl Investigative Site
state: Texas
city: Longview
country: United States
facility: Pearl Investigative Site
state: Texas
city: Lufkin
country: United States
facility: Pearl Investigative Site
state: Texas
city: New Braunfels
country: United States
facility: Pearl Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Pearl Investigative Site
state: Texas
city: Midvale
country: United States
facility: Pearl Investigative Site
state: Utah
city: Salt Lake City
country: United States
facility: Pearl Investigative Site
state: Utah
city: South Burlington
country: United States
facility: Pearl Investigative Site
state: Vermont
city: Abingdon
country: United States
facility: Pearl Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Pearl Investigative Site
state: Virginia
city: Spokane
country: United States
facility: Pearl Investigative Site
state: Washington
city: Tacoma
country: United States
facility: Pearl Investigative Site
state: Washington
city: Morgantown
country: United States
facility: Pearl Investigative Site
state: West Virginia
city: West Allis
country: United States
facility: Pearl Investigative Site
state: Wisconsin
city: New Lambton
country: Australia
facility: Pearl Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Pearl Investigative Site
state: New South Wales
city: Brisbane
country: Australia
facility: Pearl Investigative Site
state: Queensland
city: Cairns
country: Australia
facility: Pearl Investigative Site
state: Queensland
city: Wooloongabba
country: Australia
facility: Pearl Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Pearl Investigative Site
state: South Australia
city: Daw Park
country: Australia
facility: Pearl Investigative Site
state: South Australia
city: Toorak Gardens
country: Australia
facility: Pearl Investigative Site
state: South Australia
city: Box Hill
country: Australia
facility: Pearl Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Pearl Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Pearl Investigative Site
state: Western Australia
city: Perth
country: Australia
facility: Pearl Investigative Site
state: Western Australia
city: Otahuhu
country: New Zealand
facility: Pearl Investigative Site
state: Aukland
city: Caversham
country: New Zealand
facility: Pearl Investigative Site
state: Dunedin
city: Greenlane
country: New Zealand
facility: Pearl Investigative Site
state: East Aukland
city: Hamilton
country: New Zealand
facility: Pearl Investigative Site
state: Waikato
city: Newtown
country: New Zealand
facility: Pearl Investigative Site
state: Wellington
city: Tauranga
country: New Zealand
facility: Pearl Investigative Site
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Colin Reisner, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.