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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02343458
Recruitment Status : Completed
First Posted : January 22, 2015
Results First Posted : February 20, 2019
Last Update Posted : February 20, 2019
Sponsor:
Information provided by (Responsible Party):
Pearl Therapeutics, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: GFF MDI (PT003) Drug: FF MDI (PT005) Drug: GP MDI (PT001) Drug: Placebo MDI Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1756 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 30, 2015
Actual Primary Completion Date : August 31, 2017
Actual Study Completion Date : August 31, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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)
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)
Other Name: Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI; PT003); Glycopyrronium and Formoterol Fumarate Inhalation Aerosol

Experimental: FF MDI (PT005)
Formoterol Fumarate Metered Dose Inhaler (FF MDI; PT005); Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
Drug: FF MDI (PT005)
Formoterol Fumarate Metered Dose Inhaler (FF MDI; PT005); Formoterol Fumarate Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
Other Name: Formoterol Fumarate Metered Dose Inhaler (FF MDI; PT005); Formoterol Fumarate Inhalation Aerosol

Experimental: GP MDI (PT001)
Glycopyrronium Metered Dose Inhaler (GP MDI; PT001); Glycopyrronium Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
Drug: GP MDI (PT001)
Glycopyrronium Metered Dose Inhaler (GP MDI; PT001); Glycopyrronium Inhalation Aerosol administered as 2 inhalations twice-daily (BID)
Other Name: Glycopyrronium Metered Dose Inhaler (GP MDI; PT001); Glycopyrronium Inhalation Aerosol

Placebo Comparator: Placebo MDI
Placebo (matching) for GFF MDI, FF MDI, and GP MDI administered as 2 inhalations twice-daily (BID)
Drug: Placebo MDI
Placebo (matching) for GFF MDI, FF MDI, and GP MDI administered as 2 inhalations twice-daily (BID)
Other Name: Placebo (matching) for GFF MDI, FF MDI, and GP MDI




Primary Outcome Measures :
  1. Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach) [ Time Frame: at week 24 ]
    For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment

  2. Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach [ Time Frame: over weeks 12-24 ]
    Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach

  3. Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach. [ Time Frame: over 24 weeks ]
    Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach.


Secondary Outcome Measures :
  1. TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach [ Time Frame: over 24 Weeks ]
    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

  2. TDI Focal Score Over Weeks 12-24 Japan Approach [ Time Frame: over Weeks 12-24 ]
    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

  3. TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population [ Time Frame: over 24 Weeks ]
    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

  4. TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population [ Time Frame: over weeks 12-24 ]
    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

  5. Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach [ Time Frame: at week 24 ]
    Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach

  6. Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach [ Time Frame: over weeks 12-24 ]
    Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach

  7. Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach [ Time Frame: over 24 weeks ]
    Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach

  8. Change From Baseline in SGRQ Total Score at Week 24, US/China Approach [ Time Frame: at week 24 ]
    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

  9. Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach [ Time Frame: over weeks 12-24 ]
    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

  10. Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach [ Time Frame: at week 24 ]
    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

  11. Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach [ Time Frame: over weeks 12-24 ]
    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

  12. Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches [ Time Frame: over 24 weeks ]
    Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches

  13. FEV1 Measured at 5 Minutes Post-dose on Day 1 [ Time Frame: Assessed 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

  14. FEV1 Measured at 15 Minutes Post-dose on Day 1 [ Time Frame: Assessed at 15-minute 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 β2-agonists, glycopyrronium or other muscarinic anticholinergics, or any component of the MDI.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02343458


Locations
Show Show 167 study locations
Sponsors and Collaborators
Pearl Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Chair: Colin Reisner, MD Pearl Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Pearl Therapeutics, Inc.:
Study Protocol  [PDF] January 20, 2017
Statistical Analysis Plan  [PDF] March 7, 2017


Additional Information:
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Responsible Party: Pearl Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02343458    
Other Study ID Numbers: PT003014
First Posted: January 22, 2015    Key Record Dates
Results First Posted: February 20, 2019
Last Update Posted: February 20, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AstraZeneca's policy is to share data with researchers if the request is in scope of our policy. The policy and additional information can be found on astrazenecaclinicaltrials.com.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pearl Therapeutics, Inc.:
COPD
Additional relevant MeSH terms:
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Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Formoterol Fumarate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action