A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos)

COPD Clinical Trial

— KRONOS  

Official title:

A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02497001
• Other study ID #: PT010006
• Status: Completed
• Phase: Phase 3
• Start date: August 10, 2015
• Est. completion date: January 5, 2018

Study information

• Verified date: December 2020
• Source: Pearl Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease.

Description:

A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease

This study includes the following 3 sub-studies: 12-hour Pulmonary Function Test (PFT), Pharmacokinetic (PK) Profile, and Hypothalamic-pituitary-adrenal Axis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1902
• Est. completion date: January 5, 2018
• Est. primary completion date: January 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria

• Given their signed written informed consent to participate.

• 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), or other local applicable guidelines.

• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.

• Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC) ratio must be <0.70 and FEV1 must be <80% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions).

• Required COPD maintenance therapy:

• All Subjects must have been on two or more inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening. Scheduled SABA and/or scheduled SAMA are considered inhaled maintenance therapies

Please refer to the study protocol for the complete inclusion criteria list.

Exclusion Criteria

• Significant diseases or conditions other than COPD, 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 are planning to become pregnant during the course of the study, 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

• 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

• Immune suppression or severe neurological disorders affecting control of the upper airway or other risk factors that in the opinion of the Investigator would put the subject at substantial risk of pneumonia.

• Subjects with a diagnosis of narrow angle glaucoma, who, in the opinion of the Investigator, have not been adequately treated.

• Subjects who have a history of hypersensitivity to ß2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs.

Please refer to the study protocol for the complete inclusion criteria list.

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• BGF MDI 320/14.4/9.6 µg
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
• GFF MDI (PT003) 14.4/9.6 µg
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
• BFF MDI (PT009) 320/9.6 µg
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
• Symbicort® Turbuhaler® (TBH) Inhalation Powder

Locations

Country	Name	City	State
Canada	Research Site	Mirabel	Quebec
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Truro	Nova Scotia
China	Research Site	Anqing
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hohhot
China	Research Site	Huhehaote
China	Research Site	Jinan
China	Research Site	Lianyungang
China	Research Site	Linhai
China	Research Site	Nanchang
China	Research Site	Pingxiang
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shengyang
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Taiyuan
China	Research Site	Tianjin
China	Research Site	Urumchi
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuxi
China	Research Site	Xuzhou
China	Research Site	Yangzhou
China	Research Site	Yiyang Shi
China	Research Site	Zhuhai
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Date-gun
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Ginowan-shi
Japan	Research Site	Hakata-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Higashiokitama-gun
Japan	Research Site	Higashiosaka-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Iwata-shi
Japan	Research Site	Izumo-shi
Japan	Research Site	Izumo-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kahoku-gun
Japan	Research Site	Kakogawa-shi
Japan	Research Site	Kasaoka-shi
Japan	Research Site	Kasuga-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kiyose-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Kurashiki-shi
Japan	Research Site	Kure-shi
Japan	Research Site	Kure-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Mitaka-shi
Japan	Research Site	Mizunami-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Naha-shi
Japan	Research Site	Nishishirakawa-gun
Japan	Research Site	Obihiro-shi
Japan	Research Site	Ogaki-shi
Japan	Research Site	Oita-shi
Japan	Research Site	Oita-shi
Japan	Research Site	Okinawa-shi
Japan	Research Site	Ookawa-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Otsu-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Seto-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shizuoka-shi
Japan	Research Site	Suita-shi
Japan	Research Site	Tachikawa-shi
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Toyama-shi
Japan	Research Site	Toyama-shi
Japan	Research Site	Toyama-shi
Japan	Research Site	Yanagawa-shi
Japan	Research Site	Yokohama-shi
United States	Research Site	Abingdon	Virginia
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Andalusia	Alabama
United States	Research Site	Anderson	South Carolina
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dacula	Georgia
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	Fullerton	California
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Gold River	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hendersonville	North Carolina
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Jasper	Alabama
United States	Research Site	Johnson City	Tennessee
United States	Research Site	Kingwood	Texas
United States	Research Site	Longview	Texas
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	Minneapolis	Minnesota
United States	Research Site	Mooresville	North Carolina
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	Newport News	Virginia
United States	Research Site	Norcross	Georgia
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Pensacola	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Poway	California
United States	Research Site	Reno	Nevada
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Rincon	Georgia
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Rolling Hills Estates	California
United States	Research Site	Sacramento	California
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Seneca	South Carolina
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Tacoma	Washington
United States	Research Site	Tamarac	Florida
United States	Research Site	Tampa	Florida
United States	Research Site	Union	South Carolina
United States	Research Site	Wilmington	North 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,  Canada,  China,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1 AUC0-4	FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)).	at Week 24
Primary	Change From Baseline in Morning Pre-dose Trough FEV1	Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand	at Week 24
Secondary	Change From Baseline in Morning Pre-dose Trough FEV1	Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand	over 24 Weeks
Secondary	Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing	Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand	at Week 24
Secondary	Rate of Moderate or Severe COPD Exacerbations	Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand	over 24 weeks
Secondary	Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders)	Change from BGF	at Week 24
Secondary	Change From Baseline in Average Daily Rescue Ventolin HFA Use	Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand	over 24 Weeks
Secondary	Time to Onset of Action on Day 1, 5 Minutes Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1
Secondary	Time to Onset of Action on Day 1, 15 Minutes Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1
Secondary	Time to Onset of Action on Day 1, 30 Minutes Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1
Secondary	Time to Onset of Action on Day 1, 1 Hour Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1
Secondary	Time to Onset of Action on Day 1, 2 Hours Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1
Secondary	Time to Onset of Action on Day 1, 4 Hours Post Dose	FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand	Day 1

External Links

•   Related Info
•   Related Info