A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease
NCT ID: NCT03084796
Last Updated: 2021-06-15
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE2
Total Enrollment
733 participants
Study Classification
INTERVENTIONAL
Study Start Date
2017-07-28
Study Completion Date
2018-06-06
Brief Summary
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The purpose of this study is to evaluate the dose-response of different doses of CHF 5259 pMDI on lung function and other clinical outcomes, to identify the optimal dose(s) in terms of benefit/ risk ratio for further development in the target subject population.
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Detailed Description
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This is a phase II, multicenter, randomized, double-blind, placebo and active controlled dose-ranging 6-arm parallel group study to identify the optimal dose of CHF 5259 pMDI (pressurized metered dose inhaler) with respect to lung function as well as other clinical efficacy and safety outcomes.
After a 2 week run-in period under rescue albuterol and background inhaled corticosteroid (ICS) as needed, patients were randomized to one of the 6 study treatment groups. Following randomization, subjects were assessed after 3 weeks and 6 weeks of study treatment at the study center. A follow-up phone was performed a week after the last visit.
During the study, daily symptoms, rescue and background medication use and compliance with the study drug were recorded in a subject diary. Treatment-Emergent Adverse Events (TEAEs) were assessed and recorded throughout the study. At screening and subsequent visits, subjects underwent physical and vital signs examinations, spirometry measurements, and 12-lead electrocardiogram (ECG). Symptoms and chronic obstructive pulmonary disease (COPD) health status were assessed through validated questionnaires. Routine hematology, blood chemistry, and pregnancy testing were performed before enrollment and at end of study. 24-hour (24-H) digital recording of ECGs (Holter) was performed before and after the first dose and just before the last dose of study treatment.
After a 2 week run-in period under rescue albuterol and background inhaled corticosteroid (ICS) as needed, patients were randomized to one of the 6 study treatment groups. Following randomization, subjects were assessed after 3 weeks and 6 weeks of study treatment at the study center. A follow-up phone was performed a week after the last visit.
During the study, daily symptoms, rescue and background medication use and compliance with the study drug were recorded in a subject diary. Treatment-Emergent Adverse Events (TEAEs) were assessed and recorded throughout the study. At screening and subsequent visits, subjects underwent physical and vital signs examinations, spirometry measurements, and 12-lead electrocardiogram (ECG). Symptoms and chronic obstructive pulmonary disease (COPD) health status were assessed through validated questionnaires. Routine hematology, blood chemistry, and pregnancy testing were performed before enrollment and at end of study. 24-hour (24-H) digital recording of ECGs (Holter) was performed before and after the first dose and just before the last dose of study treatment.
Conditions
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COPD
Chronic Obstructive Pulmonary Disease
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
OTHER
Blinding Strategy
QUADRUPLE
Participants
Caregivers
Investigators
Outcome Assessors
Study Groups
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Treatment A
CHF 5259 pMDI 6.25 μg, 1 inhalation twice daily (bid); (total daily dose \[TDD\] of CHF 5259 12.5 μg)
Group Type
EXPERIMENTAL
CHF 5259
Intervention Type
DRUG
Dose Response: Test one of four different doses of CHF 5259
Treatment B
CHF 5259 pMDI 12.5 μg, 1 inhalation bid; (TDD of CHF 5259: 25 μg)
Group Type
EXPERIMENTAL
CHF 5259
Intervention Type
DRUG
Dose Response: Test one of four different doses of CHF 5259
Treatment C
CHF 5259 pMDI 12.5 μg, 2 inhalations bid; (TDD of CHF 5259: 50 μg)
Group Type
EXPERIMENTAL
CHF 5259
Intervention Type
DRUG
Dose Response: Test one of four different doses of CHF 5259
Treatment D
CHF 5259 pMDI 25 μg, 2 inhalations bid; (TDD of CHF 5259: 100 μg)
Group Type
EXPERIMENTAL
CHF 5259
Intervention Type
DRUG
Dose Response: Test one of four different doses of CHF 5259
Treatment E
Placebo, 2 inhalations of CHF 5259 pMDI-matched Placebo bid;
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
Placebo Control
Treatment F
Tiotropium (TIO) 18 μg, SPIRIVA® HandiHaler®, 2 inhalations once daily (od) of the content of 1 capsule; (TDD of TIO: 18 μg)
Group Type
ACTIVE_COMPARATOR
Tiotropium Bromide 18 µg Inhalation Capsule
Intervention Type
DRUG
Active Control
Interventions
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CHF 5259
Dose Response: Test one of four different doses of CHF 5259
Intervention Type
DRUG
Placebo
Placebo Control
Intervention Type
DRUG
Tiotropium Bromide 18 µg Inhalation Capsule
Active Control
Intervention Type
DRUG
Other Intervention Names
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SPIRIVA® HANDIHALER®
Eligibility Criteria
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Inclusion Criteria
* Male or female subjects aged ≥ 40 who have signed an Informed Consent Form prior to initiation of any study-related procedure.
* Subjects with a diagnosis of COPD (according to GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD Report) at least 12 months before the screening visit.
* Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
* A post-bronchodilator forced expiratory volume in the 1st second (FEV1) ≥50% and \<80% of the predicted normal value and,
* a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \< 0.7 at screening and
* a demonstrated reversibility to ipratropium defined as ΔFEV1 ≥ 5% over baseline 30-45 minutes after inhaling 4 puffs of ipratropium
* Subjects under regular COPD therapy for at least 2 months prior to screening with either inhaled long-acting muscarinic antagonist (LAMA), inhaled ICS/ long-acting β2-agonist (LABA), inhaled ICS + LAMA
* Symptomatic subjects at screening with a CAT score ≥10. This criterion must be confirmed at randomization
* Symptomatic subjects with a BDI focal score ≤ 10. This criterion must be confirmed at randomization
* A cooperative attitude and ability to demonstrate correct use of the inhalers and e-diary.
* Subjects with a diagnosis of COPD (according to GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD Report) at least 12 months before the screening visit.
* Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
* A post-bronchodilator forced expiratory volume in the 1st second (FEV1) ≥50% and \<80% of the predicted normal value and,
* a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \< 0.7 at screening and
* a demonstrated reversibility to ipratropium defined as ΔFEV1 ≥ 5% over baseline 30-45 minutes after inhaling 4 puffs of ipratropium
* Subjects under regular COPD therapy for at least 2 months prior to screening with either inhaled long-acting muscarinic antagonist (LAMA), inhaled ICS/ long-acting β2-agonist (LABA), inhaled ICS + LAMA
* Symptomatic subjects at screening with a CAT score ≥10. This criterion must be confirmed at randomization
* Symptomatic subjects with a BDI focal score ≤ 10. This criterion must be confirmed at randomization
* A cooperative attitude and ability to demonstrate correct use of the inhalers and e-diary.
Exclusion Criteria
* Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS they are willing to use highly effective birth control methods
* Diagnosis of asthma or Asthma-COPD Overlap Syndrome (ACOS) as described in global initiative for asthma (GINA) Report 2016, history of allergic rhinitis or atopy (atopy which may raise contra-indications or impact the efficacy of the study treatment according to Investigator's judgment)
* COPD Exacerbations: a moderate or severe COPD exacerbation that has not resolved ≤14 days prior to screening and ≤30 days following the last dose of any oral/systemic corticosteroid or antibiotic (whichever comes last). A Moderate or Severe COPD exacerbation during the run-in period
* Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening or during run-in
* Subjects treated with non-cardio-selective β-blockers in the month preceding screening or during the run-in period
* Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as needed
* Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
* Known respiratory disorders other than COPD which may impact the efficacy of the study treatment according the Investigator's judgment.
* Subjects who have clinically significant cardiovascular condition
* Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement
* Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) \>450 ms for males or QTcF \>470 ms for females at screening visit
* Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents
* History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study treatment according to the Investigator's judgement
* Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement
* Subjects with serum potassium levels \<3.5 mEq/L (or 3.5 mmol/L) at screening
* Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening
* Unstable or uncontrolled concurrent disease; fever, endocrine disease, gastrointestinal disease; neurological disease; hematological disease; autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgment
* History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening
* Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
* Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order.
* Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.
* Diagnosis of asthma or Asthma-COPD Overlap Syndrome (ACOS) as described in global initiative for asthma (GINA) Report 2016, history of allergic rhinitis or atopy (atopy which may raise contra-indications or impact the efficacy of the study treatment according to Investigator's judgment)
* COPD Exacerbations: a moderate or severe COPD exacerbation that has not resolved ≤14 days prior to screening and ≤30 days following the last dose of any oral/systemic corticosteroid or antibiotic (whichever comes last). A Moderate or Severe COPD exacerbation during the run-in period
* Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening or during run-in
* Subjects treated with non-cardio-selective β-blockers in the month preceding screening or during the run-in period
* Subjects treated with long-acting anti-histamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as needed
* Subjects requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
* Known respiratory disorders other than COPD which may impact the efficacy of the study treatment according the Investigator's judgment.
* Subjects who have clinically significant cardiovascular condition
* Subjects who have a clinically significant abnormal 12-lead ECG that results in active medical problem which may impact the safety of the subject according to Investigator's judgement
* Subjects whose 12-lead ECG shows Fridericia corrected QT interval (QTcF) \>450 ms for males or QTcF \>470 ms for females at screening visit
* Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that in the opinion of the Investigator would prevent use of anticholinergic agents
* History of hypersensitivity to M3 receptor antagonists, β2-adrenergic receptor agonist, corticosteroids or any of the excipients contained in any of the formulations used in the study which may raise contra-indications or impact the efficacy of the study treatment according to the Investigator's judgement
* Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study treatment according to Investigator's judgement
* Subjects with serum potassium levels \<3.5 mEq/L (or 3.5 mmol/L) at screening
* Use of potent cytochrome P450 2D6 and 3A4 inhibitors within 4 weeks prior to screening
* Unstable or uncontrolled concurrent disease; fever, endocrine disease, gastrointestinal disease; neurological disease; hematological disease; autoimmune disorders, or other which may impact the feasibility of the results of the study according to Investigator's judgment
* History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening
* Subjects who have received an investigational drug within 1 month or 5 half-lives (whichever is greater) prior to screening visit, or have been previously randomized in this trial, or are currently participating in another clinical trial.
* Subjects who are mentally or legally incapacitated, or subjects accommodated in an establishment as a result of an official or judicial order.
* Subjects who have undergone major surgery in the 3 months prior to screening visit or have a planned surgery during the trial.
Minimum Eligible Age
40 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Chiesi Farmaceutici S.p.A.
INDUSTRY
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Edward Kerwin, MD
Role: PRINCIPAL_INVESTIGATOR
Crisor LLC c/o Clinical Research Institute of Southern Oregon, Inc.
Locations
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Chiesi Investigational Site
Birmingham, Alabama, United States
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Chiesi Investigational Site
Dothan, Alabama, United States
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Montgomery, Alabama, United States
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Flagstaff, Arizona, United States
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Glendale, Arizona, United States
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Phoenix, Arizona, United States
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Phoenix, Arizona, United States
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Phoenix, Arizona, United States
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Surprise, Arizona, United States
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Tempe, Arizona, United States
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Tucson, Arizona, United States
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Anaheim, California, United States
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Escondido, California, United States
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Fullerton, California, United States
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Clinical Trials Research
Lincoln, California, United States
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Chiesi Investigational Site
Long Beach, California, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
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Newport Beach, California, United States
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San Diego, California, United States
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Tustin, California, United States
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Westminster, California, United States
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Boulder, Colorado, United States
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Centennial, Colorado, United States
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Denver, Colorado, United States
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Lafayette, Colorado, United States
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Brandon, Florida, United States
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Clearwater, Florida, United States
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Daytona Beach, Florida, United States
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Edgewater, Florida, United States
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Hialeah, Florida, United States
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Chiesi Investigational Site
Kissimmee, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Chiesi Investigational Site
Panama City, Florida, United States
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Chiesi Investigational Site
Blue Ridge, Georgia, United States
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Chiesi Investigational Site
Dacula, Georgia, United States
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Duluth, Georgia, United States
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Lawrenceville, Georgia, United States
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Marietta, Georgia, United States
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Savannah, Georgia, United States
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Chicago, Illinois, United States
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Evansville, Indiana, United States
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Valparaiso, Indiana, United States
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Louisville, Kentucky, United States
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Louisville, Kentucky, United States
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Crowley, Louisiana, United States
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Lake Charles, Louisiana, United States
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Lutherville, Maryland, United States
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Chiesi Investigational Site
Fall River, Massachusetts, United States
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Fall River, Massachusetts, United States
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Chiesi Investigational Site
Ann Arbor, Michigan, United States
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Chiesi Investigational Site
Farmington Hills, Michigan, United States
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Chiesi Investigational Site
Minneapolis, Minnesota, United States
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Chiesi Investigational Site
Saint Charles, Missouri, United States
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St Louis, Missouri, United States
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Missoula, Montana, United States
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Omaha, Nebraska, United States
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Chiesi Investigational Site
Las Vegas, Nevada, United States
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Chiesi Investigational Site
Summit, New Jersey, United States
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Chiesi Investigational Site
Albuquerque, New Mexico, United States
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Chiesi Investigational Site
The Bronx, New York, United States
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Chiesi Investigational Site
Charlotte, North Carolina, United States
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Gastonia, North Carolina, United States
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Hendersonville, North Carolina, United States
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Mooresville, North Carolina, United States
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Raleigh, North Carolina, United States
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Shelby, North Carolina, United States
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Wilmington, North Carolina, United States
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Chiesi Investigational Site
Winston-Salem, North Carolina, United States
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Cincinnati, Ohio, United States
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Chiesi Investigational Site
Columbus, Ohio, United States
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Chiesi Investigational Site
Columbus, Ohio, United States
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Clinical Research Solutions
Dayton, Ohio, United States
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Chiesi Investigational Site
Grove City, Ohio, United States
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Chiesi Investigational Site
Edmond, Oklahoma, United States
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Chiesi Investigational Site
Oklahoma City, Oklahoma, United States
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Chiesi Investigational Site
Medford, Oregon, United States
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Portland, Oregon, United States
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Chiesi Investigational Site
Philadelphia, Pennsylvania, United States
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Chiesi Investigational Site
East Providence, Rhode Island, United States
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Chiesi Investigational Site
Anderson, South Carolina, United States
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Charleston, South Carolina, United States
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Chiesi Investigational Site
Easley, South Carolina, United States
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Fort Mill, South Carolina, United States
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Chiesi Investigational Site
Gaffney, South Carolina, United States
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Chiesi Investigational Site
Greenville, South Carolina, United States
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Mt. Pleasant, South Carolina, United States
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Orangeburg, South Carolina, United States
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Rock Hill, South Carolina, United States
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Seneca, South Carolina, United States
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Spartanburg, South Carolina, United States
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Union, South Carolina, United States
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Chiesi Investigational Site
Rapid City, South Dakota, United States
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Franklin, Tennessee, United States
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Chiesi Investigational Site
Jackson, Tennessee, United States
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Chiesi Investigational Site
Knoxville, Tennessee, United States
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Chiesi Investigational Site
Tullahoma, Tennessee, United States
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Chiesi Investigational Site
Boerne, Texas, United States
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Chiesi Investigational Site
Cypress, Texas, United States
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Chiesi Investigational Site
New Braunfels, Texas, United States
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Chiesi Investigational Site
Sherman, Texas, United States
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Chiesi Investigational Site
Tomball, Texas, United States
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Chiesi Investigational Site
South Burlington, Vermont, United States
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Chiesi Investigational Site
Richmond, Virginia, United States
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Chiesi Investigational Site
Everett, Washington, United States
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Chiesi Investigational Site
Richland, Washington, United States
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Chiesi Investigational Site
Tacoma, Washington, United States
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Countries
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United States
References
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Tonnesen P. Smoking cessation and COPD. Eur Respir Rev. 2013 Mar 1;22(127):37-43. doi: 10.1183/09059180.00007212.
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van Eerd EA, van der Meer RM, van Schayck OC, Kotz D. Smoking cessation for people with chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2016 Aug 20;2016(8):CD010744. doi: 10.1002/14651858.CD010744.pub2.
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RESULT
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
https://goldcopd.org/wp-content/uploads/2017/02/wms-GOLD-2017-FINAL.pdf
From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017.
https://www.chiesi.com/en/air/
Chiesi Respiratory
https://www.chiesi.com/en/chiesi-farmaceutici-is-the-first-company-to-submit-a-marketing-authorisation-application-to-the-european-medicine-agency-for-a-triple-combination-for-the-treatment-of-copd-
Chiesi Farmaceutici is the first company to submit a marketing authorisation application to the European Medicine Agency for a Triple Combination for the treatment of COPD
https://en.wikipedia.org/wiki/Glycopyrronium_bromide
Glycopyrronium bromide
http://www.thoracic.org/members/assemblies/assemblies/srn/questionaires/bdi-tdi.php
American Thoracic Society: Baseline Dyspnea Index (BDI) \& Transition Dyspnea Index (TDI).
http://www.thoracic.org/members/assemblies/assemblies/srn/questionaires/copd.php
American Thoracic Society: COPD Assessment Test (CAT).
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CCD-05993AA3-02
Identifier Type: -
Identifier Source: org_study_id
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