Clinical trial NCT02497001: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-14
Enrollment: 1902
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: 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.

Detailed 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.

Eligibility criteria: 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 β2-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.

Primary outcomes:
measure: FEV1 AUC0-4
timeFrame: at Week 24
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
timeFrame: over 24 Weeks
measure: Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing
timeFrame: at Week 24
measure: Rate of Moderate or Severe COPD Exacerbations
timeFrame: over 24 weeks
measure: Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders)
timeFrame: at Week 24
measure: Change From Baseline in Average Daily Rescue Ventolin HFA Use
timeFrame: over 24 Weeks
measure: Time to Onset of Action on Day 1, 5 Minutes Post Dose
timeFrame: Day 1
measure: Time to Onset of Action on Day 1, 15 Minutes Post Dose
timeFrame: Day 1
measure: Time to Onset of Action on Day 1, 30 Minutes Post Dose
timeFrame: Day 1
measure: Time to Onset of Action on Day 1, 1 Hour Post Dose
timeFrame: Day 1
measure: Time to Onset of Action on Day 1, 2 Hours Post Dose
timeFrame: Day 1
measure: Time to Onset of Action on Day 1, 4 Hours Post Dose
timeFrame: Day 1
Other outcomes:
Locations:
city: Andalusia
country: United States
facility: Research Site
state: Alabama
city: Jasper
country: United States
facility: Research Site
state: Alabama
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Fullerton
country: United States
facility: Research Site
state: California
city: Gold River
country: United States
facility: Research Site
state: California
city: Poway
country: United States
facility: Research Site
state: California
city: Rolling Hills Estates
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Research Site
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
facility: Research Site
state: Florida
city: Winter Park
country: United States
facility: Research Site
state: Florida
city: Dacula
country: United States
facility: Research Site
state: Georgia
city: Norcross
country: United States
facility: Research Site
state: Georgia
city: Rincon
country: United States
facility: Research Site
state: Georgia
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Woodbury
country: United States
facility: Research Site
state: Minnesota
city: Saint Charles
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Reno
country: United States
facility: Research Site
state: Nevada
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Gastonia
country: United States
facility: Research Site
state: North Carolina
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Hendersonville
country: United States
facility: Research Site
state: North Carolina
city: Mooresville
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
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: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Dublin
country: United States
facility: Research Site
state: Ohio
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Anderson
country: United States
facility: Research Site
state: South Carolina
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Easley
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Indian Land
country: United States
facility: Research Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Rock Hill
country: United States
facility: Research Site
state: South Carolina
city: Seneca
country: United States
facility: Research Site
state: South Carolina
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Union
country: United States
facility: Research Site
state: South Carolina
city: Johnson City
country: United States
facility: Research Site
state: Tennessee
city: Kingwood
country: United States
facility: Research Site
state: Texas
city: Longview
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Abingdon
country: United States
facility: Research Site
state: Virginia
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Truro
country: Canada
facility: Research Site
state: Nova Scotia
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Mirabel
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Anqing
country: China
facility: Research Site
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
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: Changsha
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: Guangzhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Huhehaote
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Lianyungang
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Pingxiang
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: Shanghai
country: China
facility: Research Site
city: Shengyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Urumchi
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Yiyang Shi
country: China
facility: Research Site
city: Zhuhai
country: China
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Date-gun
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Ginowan-shi
country: Japan
facility: Research Site
city: Hakata-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Higashiokitama-gun
country: Japan
facility: Research Site
city: Higashiosaka-shi
country: Japan
facility: Research Site
city: Himeji-shi
country: Japan
facility: Research Site
city: Hirakata-shi
country: Japan
facility: Research Site
city: Iizuka-shi
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Iwata-shi
country: Japan
facility: Research Site
city: Izumo-shi
country: Japan
facility: Research Site
city: Izumo-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kahoku-gun
country: Japan
facility: Research Site
city: Kakogawa-shi
country: Japan
facility: Research Site
city: Kasaoka-shi
country: Japan
facility: Research Site
city: Kasuga-shi
country: Japan
facility: Research Site
city: Kishiwada-shi
country: Japan
facility: Research Site
city: Kiyose-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koga-shi
country: Japan
facility: Research Site
city: Kurashiki-shi
country: Japan
facility: Research Site
city: Kure-shi
country: Japan
facility: Research Site
city: Kure-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Maebashi-shi
country: Japan
facility: Research Site
city: Matsumoto-shi
country: Japan
facility: Research Site
city: Matsusaka-shi
country: Japan
facility: Research Site
city: Meguro-ku
country: Japan
facility: Research Site
city: Mitaka-shi
country: Japan
facility: Research Site
city: Mizunami-shi
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Naha-shi
country: Japan
facility: Research Site
city: Nishishirakawa-gun
country: Japan
facility: Research Site
city: Obihiro-shi
country: Japan
facility: Research Site
city: Ogaki-shi
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Okinawa-shi
country: Japan
facility: Research Site
city: Ookawa-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Otsu-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sakaide-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-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: Shinagawa-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shizuoka-shi
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Tachikawa-shi
country: Japan
facility: Research Site
city: Takamatsu-shi
country: Japan
facility: Research Site
city: Toon-shi
country: Japan
facility: Research Site
city: Toshima-ku
country: Japan
facility: Research Site
city: Toyama-shi
country: Japan
facility: Research Site
city: Toyama-shi
country: Japan
facility: Research Site
city: Toyama-shi
country: Japan
facility: Research Site
city: Yanagawa-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Paul Dorinsky, MD
role: STUDY_DIRECTOR
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: Liu 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.
citation: Muro 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.
citation: Huang 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.
citation: Wang 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.
citation: Ichinose 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.
citation: Dunn 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.
citation: Ferguson 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.