Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02343458
• Other study ID #: PT003014
• Status: Completed
• Phase: Phase 3
• Start date: March 30, 2015
• Est. completion date: August 31, 2017

Study information

• Verified date: January 2019
• Source: Pearl Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1756
• Est. completion date: August 31, 2017
• Est. primary completion date: August 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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 ß2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GFF MDI (PT003)
Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI; PT003); Glycopyrronium and Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
• FF MDI (PT005)
Formoterol Fumarate Metered Dose Inhaler (FF MDI; PT005); Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
• GP MDI (PT001)
Glycopyrronium Metered Dose Inhaler (GP MDI; PT001); Glycopyrronium Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
• Placebo MDI
Placebo (matching) for GFF MDI, FF MDI, and GP MDI administered as 2 inhalations twice-daily (BID)

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Hefei
China	Research Site	Hohhot
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Shijiazhuang
China	Research Site	Soochow City
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Wuxi
China	Research Site	Xiamen
China	Research Site	Xining
China	Research Site	Yiyang Shi
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Ostrava-Hrabuvka
Czechia	Research Site	Praha
Czechia	Research Site	Teplice
Germany	Research Site	Augsburg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Grosshansdof
Germany	Research Site	Hamburg
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Wiesbaden
Hungary	Research Site	Budapest
Hungary	Research Site	Gödöllo
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Siófok
Hungary	Research Site	Szeged
Japan	Research Site	Ako-shi
Japan	Research Site	Asahikawa-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hitachinaka-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kakogawa-shi
Japan	Research Site	Kamogawa-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Mito-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Naka-gun
Japan	Research Site	Ohota-ku
Japan	Research Site	Oita-shi
Japan	Research Site	Saiki-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Seto-shi
Japan	Research Site	Shimotsuga-gun
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Yanagawa-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Wonju-si
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Elblag
Poland	Research Site	Inowroclaw
Poland	Research Site	Lodz
Poland	Research Site	Lódz
Poland	Research Site	Piekary Slaskie
Poland	Research Site	Rzeszów
Poland	Research Site	Skierniewice
Poland	Research Site	Szczecin
Poland	Research Site	Tarnów
Poland	Research Site	Torun
Poland	Research Site	Warszawa Targowek
Russian Federation	Research Site	Gatchina
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Pytigorsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Sidcup
United States	Research Site	Abingdon	Virginia
United States	Research Site	Anaheim	California
United States	Research Site	Andalusia	Alabama
United States	Research Site	Atlanta	Georgia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Blue Ridge	Georgia
United States	Research Site	Boulder	Colorado
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dayton	Ohio
United States	Research Site	Dayton	Ohio
United States	Research Site	Dublin	Ohio
United States	Research Site	Easley	South Carolina
United States	Research Site	Edina	Minnesota
United States	Research Site	Foley	Alabama
United States	Research Site	Fridley	Minnesota
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Jasper	Alabama
United States	Research Site	Johnson City	Tennessee
United States	Research Site	Kissimmee	Florida
United States	Research Site	Medford	Oregon
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Panama City	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Seneca	South Carolina
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tamarac	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Union	South Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Pearl Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  China,  Czechia,  Germany,  Hungary,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach)	For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment	at week 24
Primary	Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach	Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach	over weeks 12-24
Primary	Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach.	Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach.	over 24 weeks
Secondary	TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach	TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9	over 24 Weeks
Secondary	TDI Focal Score Over Weeks 12-24 Japan Approach	TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9	over Weeks 12-24
Secondary	TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population	TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9	over 24 Weeks
Secondary	TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population	TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9	over weeks 12-24
Secondary	Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach	Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach	at week 24
Secondary	Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach	Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach	over weeks 12-24
Secondary	Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach	Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach	over 24 weeks
Secondary	Change From Baseline in SGRQ Total Score at Week 24, US/China Approach	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	at week 24
Secondary	Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach	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	over weeks 12-24
Secondary	Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach	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	at week 24
Secondary	Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach	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	over weeks 12-24
Secondary	Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches	Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches	over 24 weeks
Secondary	FEV1 Measured at 5 Minutes Post-dose on Day 1	Onset of Action as Assessed by FEV1 Day 1 at 5 Minutes Post-Dose. Reported is the FEV1 measured at 5 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant	Assessed at 5-minutes post dose on Day 1
Secondary	FEV1 Measured at 15 Minutes Post-dose on Day 1	Onset of Action as Assessed by FEV1 Day 1 at 15 Minutes Post-Dose. Reported is the FEV1 measured at 15 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant	Assessed at 15-minute post dose on Day 1

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