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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)

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ClinicalTrials.gov Identifier: NCT02497001
Recruitment Status : Completed
First Posted : July 14, 2015
Results First Posted : December 24, 2020
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
Pearl Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 8, 2015
First Posted Date  ICMJE July 14, 2015
Results First Submitted Date  ICMJE March 26, 2020
Results First Posted Date  ICMJE December 24, 2020
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE August 10, 2015
Actual Primary Completion Date January 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2020)
  • FEV1 AUC0-4 [ Time Frame: at Week 24 ]
    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)).
  • Change From Baseline in Morning Pre-dose Trough FEV1 [ Time Frame: at Week 24 ]
    Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) [ Time Frame: 24 Weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2020)
  • Change From Baseline in Morning Pre-dose Trough FEV1 [ Time Frame: over 24 Weeks ]
    Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand
  • Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing [ Time Frame: at Week 24 ]
    Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand
  • Rate of Moderate or Severe COPD Exacerbations [ Time Frame: over 24 weeks ]
    Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand
  • Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders) [ Time Frame: at Week 24 ]
    Change from BGF
  • Change From Baseline in Average Daily Rescue Ventolin HFA Use [ Time Frame: over 24 Weeks ]
    Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 5 Minutes Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 15 Minutes Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 30 Minutes Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 1 Hour Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 2 Hours Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
  • Time to Onset of Action on Day 1, 4 Hours Post Dose [ Time Frame: Day 1 ]
    FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
  • FEV1 area under the curve from 0 to 4 hours (AUC0-4) [ Time Frame: 24 Weeks ]
  • Transition dyspnea index (TDI) focal score [ Time Frame: 24 Weeks ]
  • St. George Respiratory Questionnaire (SGRQ) [ Time Frame: 24 Weeks ]
  • Rescue Ventolin HFA use [ Time Frame: 24 Weeks ]
  • Peak FEV1 within 4 hours post-dosing [ Time Frame: 24 Weeks ]
  • The EXAcerbations of Chronic pulmonary disease Tool (EXACT) total score [ Time Frame: 24 Weeks ]
  • Time to onset of action on Day 1 [ Time Frame: Day 1 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COPD
Intervention  ICMJE
  • Drug: BGF MDI 320/14.4/9.6 μg
    Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler [MDI])
    Other Name: BGF
  • Drug: GFF MDI (PT003) 14.4/9.6 μg
    Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)
    Other Name: GFF
  • Drug: BFF MDI (PT009) 320/9.6 μg
    Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)
    Other Name: BFF
  • Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder
Study Arms  ICMJE
  • Experimental: BGF MDI (PT010) 320/14.4/9.6 μg ex-actuator
    BGF MDI 320/14.4/9.6 μg,Budesonide, Glycopyrronium, Formoterol Fumarate Inhalation Aerosol
    Intervention: Drug: BGF MDI 320/14.4/9.6 μg
  • Experimental: GFF MDI (PT003) 14.4/9.6 μg ex-actuator
    GFF MDI 14.4/9.6 μg ex-actuator Glycopyrronium, Formoterol Fumarate Inhalation Aerosol
    Intervention: Drug: GFF MDI (PT003) 14.4/9.6 μg
  • Experimental: BFF MDI (PT009) 320/9.6 μg ex-actuator
    BFF MDI 320/9.6 μg, Budesonide, Formoterol Fumarate Inhalation Aerosol
    Intervention: Drug: BFF MDI (PT009) 320/9.6 μg
  • Active Comparator: Symbicort
    Symbicort® Turbuhaler® (TBH) Inhalation Powder 200/6 μg
    Intervention: Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 23, 2020)
1902
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2015)
1800
Actual Study Completion Date  ICMJE January 5, 2018
Actual Primary Completion Date January 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   China,   Japan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02497001
Other Study ID Numbers  ICMJE PT010006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Pearl Therapeutics, Inc.
Study Sponsor  ICMJE Pearl Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Paul Dorinsky, MD Pearl Therapeutics, Inc.
PRS Account Pearl Therapeutics, Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP