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)
KRONOS
1 other identifier
interventional
1,902
4 countries
190
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2015
190 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 8, 2015
CompletedFirst Posted
Study publicly available on registry
July 14, 2015
CompletedStudy Start
First participant enrolled
August 10, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 5, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 5, 2018
CompletedResults Posted
Study results publicly available
December 24, 2020
CompletedDecember 24, 2020
December 1, 2020
2.4 years
July 8, 2015
March 26, 2020
December 23, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
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
Change From Baseline in Morning Pre-dose Trough FEV1
Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand
at Week 24
Secondary Outcomes (11)
Change From Baseline in Morning Pre-dose Trough FEV1
over 24 Weeks
Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing
at Week 24
Rate of Moderate or Severe COPD Exacerbations
over 24 weeks
Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders)
at Week 24
Change From Baseline in Average Daily Rescue Ventolin HFA Use
over 24 Weeks
- +6 more secondary outcomes
Study Arms (4)
BGF MDI (PT010) 320/14.4/9.6 μg ex-actuator
EXPERIMENTALBGF MDI 320/14.4/9.6 μg,Budesonide, Glycopyrronium, Formoterol Fumarate Inhalation Aerosol
GFF MDI (PT003) 14.4/9.6 μg ex-actuator
EXPERIMENTALGFF MDI 14.4/9.6 μg ex-actuator Glycopyrronium, Formoterol Fumarate Inhalation Aerosol
BFF MDI (PT009) 320/9.6 μg ex-actuator
EXPERIMENTALBFF MDI 320/9.6 μg, Budesonide, Formoterol Fumarate Inhalation Aerosol
Symbicort
ACTIVE COMPARATORSymbicort® Turbuhaler® (TBH) Inhalation Powder 200/6 μg
Interventions
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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 β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (190)
Research Site
Andalusia, Alabama, 36420, United States
Research Site
Jasper, Alabama, 35501, United States
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Peoria, Arizona, 85381, United States
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Phoenix, Arizona, 85018, United States
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Fullerton, California, 92835, United States
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Gold River, California, 95670, United States
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Poway, California, 92064, United States
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Rolling Hills Estates, California, 90274, United States
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Sacramento, California, 95821, United States
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Clearwater, Florida, 33756, United States
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Miami, Florida, 33175, United States
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Miami, Florida, 33186, United States
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Ormond Beach, Florida, 32174, United States
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Pensacola, Florida, 32503, United States
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Tamarac, Florida, 33321, United States
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Tampa, Florida, 33603, United States
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Winter Park, Florida, 32789, United States
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Dacula, Georgia, 30019, United States
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Norcross, Georgia, 30071, United States
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Rincon, Georgia, 31326, United States
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Edina, Minnesota, 55435, United States
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Minneapolis, Minnesota, 55402, United States
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Minneapolis, Minnesota, 55407, United States
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Woodbury, Minnesota, 55125, United States
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Saint Charles, Missouri, 63301, United States
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St Louis, Missouri, 63141, United States
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Reno, Nevada, 89503, United States
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Albuquerque, New Mexico, 87108, United States
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Charlotte, North Carolina, 28207, United States
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Gastonia, North Carolina, 28054, United States
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Greensboro, North Carolina, 27408, United States
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Hendersonville, North Carolina, 28739, United States
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Mooresville, North Carolina, 28117, United States
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Wilmington, North Carolina, 28401, United States
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Winston-Salem, North Carolina, 27103, United States
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Cincinnati, Ohio, 45231, United States
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Cincinnati, Ohio, 45242, United States
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Cincinnati, Ohio, 45245, United States
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Columbus, Ohio, 43213, United States
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Columbus, Ohio, 43235, United States
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Dayton, Ohio, 45459, United States
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Dublin, Ohio, 43016, United States
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Medford, Oregon, 97504, United States
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Anderson, South Carolina, 29621, United States
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Charleston, South Carolina, 29406, United States
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Easley, South Carolina, 29640, United States
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Greenville, South Carolina, 29615, United States
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Mt. Pleasant, South Carolina, 29464, United States
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Old Point Station, South Carolina, 29707, United States
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Rock Hill, South Carolina, 29732, United States
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Seneca, South Carolina, 29678, United States
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Spartanburg, South Carolina, 29303, United States
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Union, South Carolina, 29379, United States
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Johnson City, Tennessee, 37601, United States
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Kingwood, Texas, 77339, United States
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Longview, Texas, 75605, United States
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San Antonio, Texas, 78229, United States
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Abingdon, Virginia, 24210, United States
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Newport News, Virginia, 23606, United States
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Richmond, Virginia, 23225, United States
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Richmond, Virginia, 23229, United States
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Tacoma, Washington, 98405, United States
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Morgantown, West Virginia, 26505, United States
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Truro, Nova Scotia, B2N 1L2, Canada
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Greater Sudbury, Ontario, P3A 1W8, Canada
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Mississauga, Ontario, L4V 1P1, Canada
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Toronto, Ontario, M3J 2C5, Canada
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Mirabel, Quebec, J7J 2K8, Canada
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Montreal, Quebec, H1M 1B1, Canada
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Québec, Quebec, G1V 4G5, Canada
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Trois-Rivières, Quebec, G8T 7A1, Canada
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Québec, G1W 4R4, Canada
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Anqing, 246003, China
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Baotou, 14010, China
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Beijing, 100048, China
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Beijing, 100730, China
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Beijing, 100853, China
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Beijing, CN-100029, China
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Changchun, 130021, China
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Changsha, 410002, China
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Changsha, 410011, China
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Guangzhou, 510000, China
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Guangzhou, 510120, China
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Guangzhou, 510150, China
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Guangzhou, 510180, China
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Haikou, 570311, China
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Hangzhou, 310014, China
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Heshan, 413000, China
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Hohhot, 010017, China
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Hohhot, 010050, China
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Jinan, 250013, China
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Lianyungang, 222 002, China
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Linhai, 317000, China
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Nanchang, 330006, China
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Pingxiang, 337055, China
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Shanghai, 200092, China
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Shanghai, 200120, China
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Shanghai, 200240, China
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Shanghai, 200433, China
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Shengyang, 110004, China
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Shenyang, 110001, China
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Shenyang, 110016, China
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Taiyuan, 030001, China
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Tianjin, 300052, China
Research Site
Ürümqi, 830054, China
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Wenzhou, 325027, China
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Wuhan, 430022, China
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Wuxi, 320204, China
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Xuzhou, 221006, China
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Yangzhou, 225012, China
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Zhuhai, 519099, China
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Bunkyō City, 113-8431, Japan
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Chūōku, 103-0022, Japan
Research Site
Chūōku, 103-0027, Japan
Research Site
Chūōku, 104-8560, Japan
Research Site
Date-gun, 969-1793, Japan
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Fukuoka, 814-0180, Japan
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Ginowan-shi, 901-2214, Japan
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Hakata-shi, 812-0033, Japan
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Hamamatsu, 430-0906, Japan
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Hamamatsu, 430-8525, Japan
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Hamamatsu, 434-8511, Japan
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Higashiokitama-gun, 992-0601, Japan
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Higashiosaka-shi, 577-0843, Japan
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Himeji-shi, 672-8064, Japan
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Hirakata-shi, 573-1191, Japan
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Iizuka-shi, 820-8505, Japan
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Itabashi-ku, 173-8610, Japan
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Iwata-shi, 438-8550, Japan
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Izumo-shi, 693-0068, Japan
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Izumo-shi, 693-8501, Japan
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Kagoshima, 892-0847, Japan
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Kahoku-gun, 920-0293, Japan
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Kakogawa-shi, 675-0023, Japan
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Kasaoka-shi, 714-0081, Japan
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Kasuga-shi, 816-0813, Japan
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Kishiwada-shi, 596-8501, Japan
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Kiyose-shi, 204-0023, Japan
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Kobe, 650-0017, Japan
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Koga-shi, 811-3195, Japan
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Kurashiki-shi, 711-0921, Japan
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Kure-shi, 737-0193, Japan
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Kure-shi, 737-8505, Japan
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Kyoto, 601-1434, Japan
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Kyoto, 601-8206, Japan
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Kyoto, 602-8026, Japan
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Kyoto, 607-8062, Japan
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Kyoto, 615-8087, Japan
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Maebashi, 371-0054, Japan
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Matsumoto-shi, 390-0872, Japan
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Matsusaka-shi, 515-8544, Japan
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Meguro-ku, 153-8515, Japan
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Mitaka-shi, 181-8611, Japan
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Mizunami-shi, 509-6134, Japan
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Nagaoka-shi, 940-2085, Japan
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Nagoya, 454-8502, Japan
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Nagoya, 457-8511, Japan
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Nagoya, 466-8560, Japan
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Naha, 902-0061, Japan
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Nishishirakawa-gun, 969-0213, Japan
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Obihiro-shi, 080-0013, Japan
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Ogaki-shi, 503-8502, Japan
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Okinawa-shi, 904-2143, Japan
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Ookawa-shi, 831-0016, Japan
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Osaka, 543-0035, Japan
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Osakasayama-shi, 589-8511, Japan
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Ōita, 870-0921, Japan
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Ōita, 870-0951, Japan
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Ōtsu, 520-0804, Japan
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Sakaide-shi, 762-8550, Japan
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Sakaishi, 591-8555, Japan
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Sapporo, 001-0901, Japan
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Sapporo, 064-0915, Japan
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Sendai, 980-8574, Japan
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Sendai, 983-0824, Japan
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Sendai, 984-8560, Japan
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Seto-shi, 489-8642, Japan
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Shinagawa-ku, 142-8666, Japan
Research Site
Shinjuku-ku, 162-0052, Japan
Research Site
Shizuoka, 420-8630, Japan
Research Site
Suita-shi, 564-0013, Japan
Research Site
Tachikawa-shi, 190-0014, Japan
Research Site
Takamatsu, 760-8538, Japan
Research Site
Toon-shi, 791-0281, Japan
Research Site
Toshima-ku, 171-0014, Japan
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Toyama, 930-0194, Japan
Research Site
Toyama, 931-8533, Japan
Research Site
Toyama, 939-8282, Japan
Research Site
Yanagawa-shi, 832-0059, Japan
Research Site
Yokohama, 236-0004, Japan
Related Publications (12)
Patel M, Marshall J, Martinez FJ, Mushunje A, Bowen K, Jenkins M. Frequent productive cough in COPD relates to exacerbation risk and treatment benefit from budesonide/glycopyrrolate/formoterol fumarate: a post hoc analysis of KRONOS. Respir Med. 2025 Dec;250:108499. doi: 10.1016/j.rmed.2025.108499. Epub 2025 Nov 12.
PMID: 41237914DERIVEDSingh D, Bafadhel M, Arya N, Marshall J, Parikh H, Kisielewicz D, Movitz C, Bowen K, Patel M. Step up to triple therapy versus switch to dual bronchodilator therapy in patients with COPD on an inhaled corticosteroid/long-acting beta2-agonist: post-hoc analyses of KRONOS. Respir Res. 2025 May 8;26(1):175. doi: 10.1186/s12931-025-03234-5.
PMID: 40340809DERIVEDMuro S, Seki M, Hurst JR, Petullo D, Marshall J, Bowen K, Darken PF, Duncan EA, Megally A, Patel M. Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies for Patients with COPD and Phenotypic Features of Asthma: A Pooled Post Hoc Analysis of KRONOS and ETHOS. Int J Chron Obstruct Pulmon Dis. 2024 Dec 12;19:2729-2737. doi: 10.2147/COPD.S478349. eCollection 2024.
PMID: 39691156DERIVEDMuro S, Kawayama T, Sugiura H, Seki M, Duncan EA, Bowen K, Marshall J, Megally A, Patel M. Benefits of budesonide/glycopyrronium/formoterol fumarate dihydrate on lung function and exacerbations of COPD: a post-hoc analysis of the KRONOS study by blood eosinophil level and exacerbation history. Respir Res. 2024 Aug 5;25(1):297. doi: 10.1186/s12931-024-02918-8.
PMID: 39103901DERIVEDSingh 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.
PMID: 35815359DERIVEDLiu J, He X, Wu J. Economic Evaluation of Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate for the Treatment of Moderate to Very Severe Chronic Obstructive Pulmonary Disease in China Using a Semi-Markov Model. Appl Health Econ Health Policy. 2022 Sep;20(5):743-755. doi: 10.1007/s40258-022-00732-1. Epub 2022 Apr 28.
PMID: 35478081DERIVEDMuro S, Sugiura H, Darken P, Dorinsky P. Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts. Respir Res. 2021 Jun 28;22(1):187. doi: 10.1186/s12931-021-01773-1.
PMID: 34182998DERIVEDHuang Y, Assam PN, Feng C, Su R, Dorinsky P, Gillen M. Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects. Pulm Pharmacol Ther. 2020 Oct;64:101976. doi: 10.1016/j.pupt.2020.101976. Epub 2020 Nov 2.
PMID: 33152467DERIVEDWang C, Yang T, Kang J, Chen R, Zhao L, He H, Assam PN, Su R, Bourne E, Ballal S, DeAngelis K, Dorinsky P. Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in Chinese Patients with COPD: A Subgroup Analysis of KRONOS. Adv Ther. 2020 Apr;37(4):1591-1607. doi: 10.1007/s12325-020-01266-5. Epub 2020 Mar 6.
PMID: 32152869DERIVEDIchinose M, Fukushima Y, Inoue Y, Hataji O, Ferguson GT, Rabe KF, Hayashi N, Okada H, Takikawa M, Bourne E, Ballal S, DeAngelis K, Aurivillius M, Reisner C, Dorinsky P. Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD. Int J Chron Obstruct Pulmon Dis. 2019 Dec 23;14:2993-3002. doi: 10.2147/COPD.S220861. eCollection 2019.
PMID: 31920296DERIVEDDunn LJ, Kerwin EM, DeAngelis K, Darken P, Gillen M, Dorinsky P. Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. Pulm Pharmacol Ther. 2020 Feb;60:101873. doi: 10.1016/j.pupt.2019.101873. Epub 2019 Dec 10.
PMID: 31841699DERIVEDFerguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M, Bourne E, Ballal S, Darken P, DeAngelis K, Aurivillius M, Dorinsky P, Reisner C. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018 Oct;6(10):747-758. doi: 10.1016/S2213-2600(18)30327-8. Epub 2018 Sep 16.
PMID: 30232048DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pearl Therapeutics Inc.
- Organization
- Pearl Therapeutics Inc.
Study Officials
- STUDY DIRECTOR
Paul Dorinsky, MD
Pearl Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 8, 2015
First Posted
July 14, 2015
Study Start
August 10, 2015
Primary Completion
January 5, 2018
Study Completion
January 5, 2018
Last Updated
December 24, 2020
Results First Posted
December 24, 2020
Record last verified: 2020-12
Data Sharing
- IPD Sharing
- Will share