Clinical trial NCT02343458: Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD
Official title: A Randomized, Double-Blind, 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
Keywords: COPD
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-22
Enrollment: 1756
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: A chronic dosing (24 weeks) study to assess the efficacy and safety GFF MDI; PT003), FF MDI; PT005, and GP MDI; PT001) in subjects with moderate to very severe COPD, compared with placebo.

Detailed description: A randomized, double-blind, chronic dosing (24 weeks), placebo-controlled, parallel group, multi-center study to assess the efficacy and safety of glycopyrronium and formoterol fumarate inhalation aerosol (GFF; PT003), formoterol fumarate inhalation aerosol (FF; PT005), and glycopyrronium inhalation aerosol (GP; PT001) in subjects with moderate to very severe COPD, compared with placebo.

Eligibility criteria: Inclusion Criteria:

* Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study.
* 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.
* Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of \<0.70.
* FEV1 must be \<80% predicted normal value calculated using the Third National Health and Nutrition Examination Survey (NHANES III) reference equations. (Or reference norms applicable to other regions).

Exclusion Criteria:

* Significant diseases other than COPD, ie, disease or condition which, in the opinion of the Investigator, may put the subject 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.
* Women who are pregnant or lactating or women of childbearing potential who are not using an acceptable method of contraception.
* Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.
* Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening) or during the Screening Period (Visit 1 to Visit 4).
* Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Visit 1 (Screening) or during the Screening Period (Visit 1 to Visit 4).
* Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible.
* Subjects who have a history of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI.

Primary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach)
timeFrame: at week 24
measure: Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach
timeFrame: over weeks 12-24
measure: Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach.
timeFrame: over 24 weeks
Secondary outcomes:
measure: TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach
timeFrame: over 24 Weeks
measure: TDI Focal Score Over Weeks 12-24 Japan Approach
timeFrame: over Weeks 12-24
measure: TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population
timeFrame: over 24 Weeks
measure: TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population
timeFrame: over weeks 12-24
measure: Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach
timeFrame: at week 24
measure: Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach
timeFrame: over weeks 12-24
measure: Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach
timeFrame: over 24 weeks
measure: Change From Baseline in SGRQ Total Score at Week 24, US/China Approach
timeFrame: at week 24
measure: Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach
timeFrame: over weeks 12-24
measure: Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach
timeFrame: at week 24
measure: Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach
timeFrame: over weeks 12-24
measure: Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches
timeFrame: over 24 weeks
measure: FEV1 Measured at 5 Minutes Post-dose on Day 1
timeFrame: Assessed at 5-minutes post dose on Day 1
measure: FEV1 Measured at 15 Minutes Post-dose on Day 1
timeFrame: Assessed at 15-minute post dose on Day 1
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Research Site
state: Alabama
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Foley
country: United States
facility: Research Site
state: Alabama
city: Jasper
country: United States
facility: Research Site
state: Alabama
city: Anaheim
country: United States
facility: Research Site
state: California
city: Boulder
country: United States
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state: Colorado
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Miami
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state: Florida
city: Miami
country: United States
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state: Florida
city: Panama City
country: United States
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state: Florida
city: Pensacola
country: United States
facility: Research Site
state: Florida
city: Tamarac
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
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state: Florida
city: Winter Park
country: United States
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state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Blue Ridge
country: United States
facility: Research Site
state: Georgia
city: North Dartmouth
country: United States
facility: Research Site
state: Massachusetts
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: Fridley
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
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state: Minnesota
city: Woodbury
country: United States
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state: Minnesota
city: Saint Charles
country: United States
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state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Gastonia
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Columbus
country: United States
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state: Ohio
city: Dayton
country: United States
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state: Ohio
city: Dayton
country: United States
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state: Ohio
city: Dublin
country: United States
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state: Ohio
city: Oklahoma City
country: United States
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state: Oklahoma
city: Medford
country: United States
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state: Oregon
city: Easley
country: United States
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state: South Carolina
city: Gaffney
country: United States
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state: South Carolina
city: Greenville
country: United States
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state: South Carolina
city: Rock Hill
country: United States
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state: South Carolina
city: Seneca
country: United States
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state: South Carolina
city: Spartanburg
country: United States
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state: South Carolina
city: Union
country: United States
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state: South Carolina
city: Johnson City
country: United States
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state: Tennessee
city: Abingdon
country: United States
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state: Virginia
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shengyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Soochow City
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xining
country: China
facility: Research Site
city: Yiyang Shi
country: China
facility: Research Site
city: Jindrichuv Hradec
country: Czechia
facility: Research Site
city: Ostrava-Hrabuvka
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Teplice
country: Czechia
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Grosshansdof
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gödöllő
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Siófok
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Ako-shi
country: Japan
facility: Research Site
city: Asahikawa-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Himeji-shi
country: Japan
facility: Research Site
city: Himeji-shi
country: Japan
facility: Research Site
city: Hitachinaka-shi
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Kakogawa-shi
country: Japan
facility: Research Site
city: Kamogawa-shi
country: Japan
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city: Kanazawa-shi
country: Japan
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city: Kishiwada-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
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city: Koga-shi
country: Japan
facility: Research Site
city: Matsumoto-shi
country: Japan
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city: Matsumoto-shi
country: Japan
facility: Research Site
city: Mito-shi
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Naka-gun
country: Japan
facility: Research Site
city: Ohota-ku
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Saiki-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Seto-shi
country: Japan
facility: Research Site
city: Shimotsuga-gun
country: Japan
facility: Research Site
city: Takamatsu-shi
country: Japan
facility: Research Site
city: Toon-shi
country: Japan
facility: Research Site
city: Yanagawa-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Elbląg
country: Poland
facility: Research Site
city: Inowrocław
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Piekary Śląskie
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Skierniewice
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Tarnów
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Warszawa Targowek
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Gatchina
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Pytigorsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Northwood
country: United Kingdom
facility: Research Site
city: Sidcup
country: United Kingdom
facility: Research Site
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: Chen R, Zhong N, Wang HY, Zhao L, Mei X, Qin Z, Huang J, Assam PN, Maes A, Siddiqui S, Martin UJ, Reisner C. Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD. Int J Chron Obstruct Pulmon Dis. 2020 Jan 8;15:43-56. doi: 10.2147/COPD.S223638. eCollection 2020.