Clinical trial NCT01854658: Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD (PINNACLE 2)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-15
Enrollment: 1615
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: 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.


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.
* 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

Primary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1
timeFrame: At Week 24
Secondary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks
timeFrame: Over 24 weeks
measure: Peak FEV1
timeFrame: At week 24
measure: St. George Respiratory Questionnaire (SGRQ) Score
timeFrame: 24 weeks
measure: Rescue Ventolin HFA Use
timeFrame: 24 weeks
measure: Onset of Action as Assessed by FEV1
timeFrame: Day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Florence
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Jasper
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Mobile
country: United States
facility: Pearl Investigative Site
state: Alabama
city: Fullerton
country: United States
facility: Pearl Investigative Site
state: California
city: Gold River
country: United States
facility: Pearl Investigative Site
state: California
city: Long Beach
country: United States
facility: Pearl Investigative Site
state: California
city: Los Angeles
country: United States
facility: Pearl Investigative Site
state: California
city: Mission Hills
country: United States
facility: Pearl Investigative Site
state: California
city: Newport Beach
country: United States
facility: Pearl Investigative Site
state: California
city: North Hollywood
country: United States
facility: Pearl Investigative Site
state: California
city: Northridge
country: United States
facility: Pearl Investigative Site
state: California
city: Rancho Mirage
country: United States
facility: Pearl Investigative Site
state: California
city: Rialto
country: United States
facility: Pearl Investigative Site
state: California
city: Rolling Hills Estates
country: United States
facility: Pearl Investigative Site
state: California
city: San Diego
country: United States
facility: Pearl Investigative Site
state: California
city: Santa Monica
country: United States
facility: Pearl Investigative Site
state: California
city: Stockton
country: United States
facility: Pearl Investigative Site
state: California
city: Torrance
country: United States
facility: Pearl Investigative Site
state: California
city: Wildomar
country: United States
facility: Pearl Investigative Site
state: California
city: Centennial
country: United States
facility: Pearl Investigative Site
state: Colorado
city: Boynton Beach
country: United States
facility: Pearl Investigative Site
state: Florida
city: Clearwater
country: United States
facility: Pearl Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Pearl Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Pearl Investigative Site
state: Florida
city: Kissimmee
country: United States
facility: Pearl Investigative Site
state: Florida
city: Melbourne
country: United States
facility: Pearl Investigative Site
state: Florida
city: Miami
country: United States
facility: Pearl Investigative Site
state: Florida
city: New Port Richey
country: United States
facility: Pearl Investigative Site
state: Florida
city: Orlando
country: United States
facility: Pearl Investigative Site
state: Florida
city: Ormond Beach
country: United States
facility: Pearl Investigative Site
state: Florida
city: Port Orange
country: United States
facility: Pearl Investigative Site
state: Florida
city: Sanford
country: United States
facility: Pearl Investigative Site
state: Florida
city: Sebring
country: United States
facility: Pearl Investigative Site
state: Florida
city: Tamarac
country: United States
facility: Pearl Investigative Site
state: Florida
city: Winter Park
country: United States
facility: Pearl Investigative Site
state: Florida
city: Lawrenceville
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Norcross
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Smyrna
country: United States
facility: Pearl Investigative Site
state: Georgia
city: Elk Grove
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Normal
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Peoria
country: United States
facility: Pearl Investigative Site
state: Illinois
city: Evansville
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Franklin
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Lafayette
country: United States
facility: Pearl Investigative Site
state: Indiana
city: South Bend
country: United States
facility: Pearl Investigative Site
state: Indiana
city: Council Bluffs
country: United States
facility: Pearl Investigative Site
state: Iowa
city: Hazard
country: United States
facility: Pearl Investigative Site
state: Kentucky
city: Louisville
country: United States
facility: Pearl Investigative Site
state: Kentucky
city: Paducah
country: United States
facility: Pearl Investigative Site
state: Kentucky
city: Lake Charles
country: United States
facility: Pearl Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Pearl Investigative Siteq
state: Maryland
city: Columbia
country: United States
facility: Pearl Investigative Site
state: Maryland
city: Haverhill
country: United States
facility: Pearl Investigative Site
state: Massachusetts
city: North Dartmouth
country: United States
facility: Pearl Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Pearl Investigative Site
state: Michigan
city: Fridley
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Minneapolis
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: Rochester
country: United States
facility: Pearl Investigative Site
state: Minnesota
city: St Charles
country: United States
facility: Pearl Investigative Site
state: Missouri
city: St Louis
country: United States
facility: Pearl Investigative Site
state: Missouri
city: St. Louis
country: United States
facility: Pearl Investigative Site
state: Missouri
city: Fremont
country: United States
facility: Pearl Investigative Site
state: Nebraska
city: Omaha
country: United States
facility: Pearl Investigative Site
state: Nebraska
city: Henderson
country: United States
facility: Pearl Investigative Site
state: Nevada
city: Newington
country: United States
facility: Pearl Investigative Site
state: New Hampshire
city: Cedar Knolls
country: United States
facility: Pearl Investigative Site
state: New Jersey
city: Marlton
country: United States
facility: Pearl Investigative Site
state: New Jersey
city: Buffalo
country: United States
facility: Pearl Investigative Site
state: New York
city: New York
country: United States
facility: Pearl Investigative Site
state: New York
city: Rochester
country: United States
facility: Pearl Investigative Site
state: New York
city: Boone
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Hendersonville
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Raleigh
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Akron
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Canton
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Cincinnati
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Willoughby
country: United States
facility: Pearl Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Pearl Investigative Site
state: Oklahoma
city: Tulsa
country: United States
facility: Pearl Investigative Site
state: Oklahoma
city: Portland
country: United States
facility: Pearl Investigative Site
state: Oregon
city: Hershey
country: United States
facility: Pearl Investigative Site
state: Pennsylvania
city: Phoenixville
country: United States
facility: Pearl Investigative Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pearl Investigative Site
state: Pennsylvania
city: Anderson
country: United States
facility: Pearl Investigative Site
state: South Carolina
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: Fort Mill
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: Rock Hill
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Seneca
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Spartanburg
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Nashville
country: United States
facility: Pearl Investigative Site
state: Tennessee
city: Arlington
country: United States
facility: Pearl Investigative Site
state: Texas
city: Beaumont
country: United States
facility: Pearl Investigative Site
state: Texas
city: Boerne
country: United States
facility: Pearl Investigative Site
state: Texas
city: Corsicana
country: United States
facility: Pearl Investigative Site
state: Texas
city: Dallas
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: San Antonio
country: United States
facility: Pearl Investigative Site
state: Texas
city: Tomball
country: United States
facility: Pearl Investigative Site
state: Texas
city: Waco
country: United States
facility: Pearl Investigative Site
state: Texas
city: Midlothian
country: United States
facility: Pearl Investigative Site
state: Virginia
city: Newport News
country: United States
facility: Pearl Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Pearl Investigative Site
state: Virginia
city: Ricmond
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: Bridgeport
country: United States
facility: Pearl Investigative Site
state: West Virginia
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Colin Reisner, MD
role: STUDY_CHAIR
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.