A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease (GLIMMER)

May 20, 2021 updated by: Chiesi Farmaceutici S.p.A.

A 6-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 5259 pMDI (HFA Glycopyrronium Bromide Via Pressurized Metered Dose Inhaler) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

733

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35244
        • Chiesi Investigational Site
      • Dothan, Alabama, United States, 36305
        • Chiesi Investigational Site
      • Montgomery, Alabama, United States, 36106
        • Chiesi Investigational Site
    • Arizona
      • Flagstaff, Arizona, United States, 86001
        • Chiesi Investigational Site
      • Glendale, Arizona, United States, 85306
        • Chiesi Investigational Site
      • Phoenix, Arizona, United States, 85014
        • Chiesi Investigational Site
      • Phoenix, Arizona, United States, 85006
        • Chiesi Investigational Site
      • Phoenix, Arizona, United States, 85018
        • Chiesi Investigational Site
      • Surprise, Arizona, United States, 85374
        • Chiesi Investigational Site
      • Tempe, Arizona, United States, 85283
        • Chiesi Investigational Site
      • Tucson, Arizona, United States, 85710
        • Chiesi Investigational Site
    • California
      • Anaheim, California, United States, 92801
        • Chiesi Investigational Site
      • Escondido, California, United States, 92025
        • Chiesi Investigational Site
      • Fullerton, California, United States, 92835
        • Chiesi Investigational Site
      • Lincoln, California, United States, 95648
        • Clinical Trials Research
      • Long Beach, California, United States, 90806
        • Chiesi Investigational Site
      • Los Angeles, California, United States, 90017
        • Chiesi Investigational Site
      • Los Angeles, California, United States, 90048
        • Chiesi Investigational Site
      • Los Angeles, California, United States, 90036
        • Chiesi Investigational Site
      • Newport Beach, California, United States, 92663
        • Chiesi Investigational Site
      • San Diego, California, United States, 92120
        • Chiesi Investigational Site
      • Tustin, California, United States, 92780
        • Chiesi Investigational Site
      • Westminster, California, United States, 92683
        • Chiesi Investigational Site
    • Colorado
      • Boulder, Colorado, United States, 80301
        • Chiesi Investigational Site
      • Centennial, Colorado, United States, 80112
        • Chiesi Investigational Site
      • Denver, Colorado, United States, 80230
        • Chiesi Investigational Site
      • Lafayette, Colorado, United States, 80026
        • Chiesi Investigational Site
    • Florida
      • Brandon, Florida, United States, 33511
        • Chiesi Investigational Site
      • Clearwater, Florida, United States, 33765
        • Chiesi Investigational Site
      • Daytona Beach, Florida, United States, 32117
        • Chiesi Investigational Site
      • Edgewater, Florida, United States, 32132
        • Chiesi Investigational Site
      • Hialeah, Florida, United States, 33012
        • Chiesi Investigational Site
      • Kissimmee, Florida, United States, 34741
        • Chiesi Investigational Site
      • Miami, Florida, United States, 33144
        • Chiesi Investigational Site
      • Miami, Florida, United States, 33165
        • Chiesi Investigational Site
      • Miami, Florida, United States, 33176
        • Chiesi Investigational Site
      • Miami, Florida, United States, 33186
        • Chiesi Investigational Site
      • Orlando, Florida, United States, 32825
        • Chiesi Investigational Site
      • Panama City, Florida, United States, 32405
        • Chiesi Investigational Site
    • Georgia
      • Blue Ridge, Georgia, United States, 30513
        • Chiesi Investigational Site
      • Dacula, Georgia, United States, 30019
        • Chiesi Investigational Site
      • Duluth, Georgia, United States, 30096
        • Chiesi Investigational Site
      • Lawrenceville, Georgia, United States, 30046
        • Chiesi Investigational Site
      • Marietta, Georgia, United States, 30060
        • Chiesi Investigational Site
      • Savannah, Georgia, United States, 31405
        • Chiesi Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Chiesi Investigational Site
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Chiesi Investigational Site
      • Valparaiso, Indiana, United States, 46383
        • Chiesi Investigational Site
    • Kentucky
      • Louisville, Kentucky, United States, 40215
        • Chiesi Investigational Site
      • Louisville, Kentucky, United States, 40218
        • Chiesi Investigational Site
    • Louisiana
      • Crowley, Louisiana, United States, 70526
        • Chiesi Investigational Site
      • Lake Charles, Louisiana, United States, 70601
        • Chiesi Investigational Site
    • Maryland
      • Lutherville, Maryland, United States, 21093
        • Chiesi Investigational Site
    • Massachusetts
      • Fall River, Massachusetts, United States, 02720
        • Chiesi Investigational Site
      • Fall River, Massachusetts, United States, 02721
        • Chiesi Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Chiesi Investigational Site
      • Farmington Hills, Michigan, United States, 48336
        • Chiesi Investigational Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55402
        • Chiesi Investigational Site
    • Missouri
      • Saint Charles, Missouri, United States, 63301
        • Chiesi Investigational Site
      • Saint Louis, Missouri, United States, 63141
        • Chiesi Investigational Site
    • Montana
      • Missoula, Montana, United States, 59808
        • Chiesi Investigational Site
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Chiesi Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89119
        • Chiesi Investigational Site
    • New Jersey
      • Summit, New Jersey, United States, 07901
        • Chiesi Investigational Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87108
        • Chiesi Investigational Site
    • New York
      • Bronx, New York, United States, 10455
        • Chiesi Investigational Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Chiesi Investigational Site
      • Gastonia, North Carolina, United States, 28054
        • Chiesi Investigational Site
      • Hendersonville, North Carolina, United States, 28739
        • Chiesi Investigational Site
      • Mooresville, North Carolina, United States, 28117
        • Chiesi Investigational Site
      • Raleigh, North Carolina, United States, 27607
        • Chiesi Investigational Site
      • Shelby, North Carolina, United States, 28150
        • Chiesi Investigational Site
      • Wilmington, North Carolina, United States, 28401
        • Chiesi Investigational Site
      • Winston-Salem, North Carolina, United States, 27103
        • Chiesi Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Chiesi Investigational Site
      • Columbus, Ohio, United States, 43213
        • Chiesi Investigational Site
      • Columbus, Ohio, United States, 43215
        • Chiesi Investigational Site
      • Dayton, Ohio, United States, 45409
        • Clinical Research Solutions
      • Grove City, Ohio, United States, 43123
        • Chiesi Investigational Site
    • Oklahoma
      • Edmond, Oklahoma, United States, 73034
        • Chiesi Investigational Site
      • Oklahoma City, Oklahoma, United States, 73103
        • Chiesi Investigational Site
    • Oregon
      • Medford, Oregon, United States, 97504
        • Chiesi Investigational Site
      • Portland, Oregon, United States, 97202
        • Chiesi Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Chiesi Investigational Site
    • Rhode Island
      • East Providence, Rhode Island, United States, 02914
        • Chiesi Investigational Site
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Chiesi Investigational Site
      • Charleston, South Carolina, United States, 29406
        • Chiesi Investigational Site
      • Easley, South Carolina, United States, 29640
        • Chiesi Investigational Site
      • Fort Mill, South Carolina, United States, 29707
        • Chiesi Investigational Site
      • Gaffney, South Carolina, United States, 29340
        • Chiesi Investigational Site
      • Greenville, South Carolina, United States, 29615
        • Chiesi Investigational Site
      • Mount Pleasant, South Carolina, United States, 29464
        • Chiesi Investigational Site
      • Orangeburg, South Carolina, United States, 29118
        • Chiesi Investigational Site
      • Rock Hill, South Carolina, United States, 29732
        • Chiesi Investigational Site
      • Seneca, South Carolina, United States, 29678
        • Chiesi Investigational Site
      • Spartanburg, South Carolina, United States, 29303
        • Chiesi Investigational Site
      • Union, South Carolina, United States, 29379
        • Chiesi Investigational Site
    • South Dakota
      • Rapid City, South Dakota, United States, 57702
        • Chiesi Investigational Site
    • Tennessee
      • Franklin, Tennessee, United States, 37067
        • Chiesi Investigational Site
      • Jackson, Tennessee, United States, 38305
        • Chiesi Investigational Site
      • Knoxville, Tennessee, United States, 37909
        • Chiesi Investigational Site
      • Tullahoma, Tennessee, United States, 37388
        • Chiesi Investigational Site
    • Texas
      • Boerne, Texas, United States, 78006
        • Chiesi Investigational Site
      • Cypress, Texas, United States, 77429
        • Chiesi Investigational Site
      • New Braunfels, Texas, United States, 78130
        • Chiesi Investigational Site
      • Sherman, Texas, United States, 75092
        • Chiesi Investigational Site
      • Tomball, Texas, United States, 77375
        • Chiesi Investigational Site
    • Vermont
      • South Burlington, Vermont, United States, 05403
        • Chiesi Investigational Site
    • Virginia
      • Richmond, Virginia, United States, 23225
        • Chiesi Investigational Site
    • Washington
      • Everett, Washington, United States, 98208
        • Chiesi Investigational Site
      • Richland, Washington, United States, 99352
        • Chiesi Investigational Site
      • Tacoma, Washington, United States, 98405
        • Chiesi Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment A
CHF 5259 pMDI 6.25 μg, 1 inhalation twice daily (bid); (total daily dose [TDD] of CHF 5259 12.5 μg)
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259
EXPERIMENTAL: Treatment B
CHF 5259 pMDI 12.5 μg, 1 inhalation bid; (TDD of CHF 5259: 25 μg)
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259
EXPERIMENTAL: Treatment C
CHF 5259 pMDI 12.5 μg, 2 inhalations bid; (TDD of CHF 5259: 50 μg)
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259
EXPERIMENTAL: Treatment D
CHF 5259 pMDI 25 μg, 2 inhalations bid; (TDD of CHF 5259: 100 μg)
Drug: CHF 5259
Dose Response: Test one of four different doses of CHF 5259
PLACEBO_COMPARATOR: Treatment E
Placebo, 2 inhalations of CHF 5259 pMDI-matched Placebo bid;
Drug: Placebo
Placebo Control
ACTIVE_COMPARATOR: Treatment F
Tiotropium (TIO) 18 μg, SPIRIVA® HandiHaler®, 2 inhalations once daily (od) of the content of 1 capsule; (TDD of TIO: 18 μg)
Drug: Tiotropium Bromide 18 µg Inhalation Capsule
Active Control
Other Names:
  • SPIRIVA® HANDIHALER®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6
Time Frame: Baseline, Week 6

Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6).

Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours).

Definitions:

AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Baseline, Week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1
Time Frame: Baseline, Day 1

Change from baseline in FEV1 AUC(0-12h), normalized by time, on Day 1.

Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours).

Definitions:

AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Baseline, Day 1
Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Time Frame: Baseline, Day 1, Week 6

Change from baseline in FEV1 AUC(0-4h), normalized by time on Day 1 of treatment (Week 0).

Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 and at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (4 hours).

Definitions:

AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-4h)=Mean FEV1 after inhalation, measured at prespecified times for up to 4-h observation period (0-4h), normalized by time;
Baseline, Day 1, Week 6
Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6
Time Frame: Baseline, Day 1, Week 6

Change from baseline in FEV1 peak(0-4h) (L) on Day 1 and at Week 6.

Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication.

Definitions:

Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; Peak(0-4h)=Maximum FEV1 between 0 and 4 h.
Baseline, Day 1, Week 6
Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6
Time Frame: Baseline, Day 1, Week 6

Change from baseline in FVC AUC(0-12h), normalized by time, on Day 1 and at the end of treatment (Week 6).

Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours).

Definitions:

AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-12h)=Mean FVC after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Baseline, Day 1, Week 6
Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Time Frame: Baseline, Day 1, Week 6

Change from baseline in FVC AUC(0-4h), normalized by time, on Day 1 and at the end of treatment (Week 6).

Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours).

Definitions:

AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-4)=Mean FVC after inhalation, measured at prespecified times for up to 4-h observation period (0-4 h), normalized by time;
Baseline, Day 1, Week 6
Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6
Time Frame: Baseline, Day 1, Week 6

Change from baseline in FVC peak(0-4h) (L) on Day 1 and at the end of treatment at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication.

Definitions:

Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; Peak(0-4h)=Maximum FEV1 between 0 and 4 h.
Baseline, Day 1, Week 6
Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1
Time Frame: Day 1
Time to onset of action is defined as the time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥100 mL.
Day 1
Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1
Time Frame: Day 1
Number of patients achieving onset of action was defined as a change from baseline in post-dose FEV1 ≥100 mL on Day 1. These are the patients who contributed to the results, reported as median and 95% CI for 'time to onset of action' presented in Outcome Measure 8, above.
Day 1
Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6
Time Frame: Baseline, Week 3, Week 6

Change from baseline in FEV1 at treatment visit 3 (Week 3) and treatment visit 4 (Week 6) of treatment. Spirometry, used to measure FEV1, was performed according to internationally accepted standards.

Definitions:

Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second;
Baseline, Week 3, Week 6
Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6
Time Frame: Baseline, Week 3, Week 6

Change from baseline in IC at treatment Visit 3 (Week 3) and treatment Visit 4 (Week 6). Spirometry was used to measure IC and was performed according to internationally accepted standards.

Definitions:

Baseline: value of the measurement recorded at 45 mins pre-dose at Visit 2 (Week 0); IC=Inspiratory capacity;
Baseline, Week 3, Week 6
Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6
Time Frame: Baseline, Week 3, Week 6

Number of subjects achieving TDI focal score ≥1, at treatment visit 3 (Week 3) and at treatment visit 4 (Week 6).

TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement); total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important.

Definitions:

Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;
Baseline, Week 3, Week 6
Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6
Time Frame: Baseline, Week 3, Week 6

Transitional Dyspnea Index (TDI) focal score at treatment visit 3 (Week 3) and treatment visit 4 (Week 6).

TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement), with a total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important.

Definitions:

Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;
Baseline, Week 3, Week 6
Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period
Time Frame: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Evaluate the number of rescue medication-free days compared with baseline. Results are shown as percentage (%) of rescue medication-free days; an increased value indicates improvement from baseline.

Definitions:

Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3, Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0).
Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period
Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period
Time Frame: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Evaluate the change from baseline in average use of rescue medication (number of puffs/day) during the inter-visit periods and the entire treatment period.

Results are shown as number of puffs/day; a decrease (implies improvement) from baseline in average use of rescue medication.

Definitions:

Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3 (Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0);
Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period
Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period
Time Frame: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period

Change from baseline in average EXACT-Respiratory Symptom (E-RS) total score during inter-visit periods and the entire treatment period

E-RS in COPD uses 11 respiratory symptom items from the 14-item EXAcerbations of COPD tool (EXACT). E-RS total score quantifies respiratory symptom severity on a scale ranging from 0 to 40. Higher E-RS total scores indicate more severe symptoms and a declining total score indicates health improvement. E-RS questionnaire was completed by the patient each evening (e-diary).

Definitions:

For details on baseline, inter-visit periods, and the entire treatment period, please refer to outcome measure #15.
Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment period
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
Time Frame: Baseline, Day 1, Week 6

Vital signs -- Systolic blood pressure (SBP), Diastolic blood pressure (DBP) were measured at prespecified times, using a 12-Lead single ECGs were recorded at all study visits (pre-dose at V1 (Week -2) and V3 (Week 3), as well as at pre-dose and 1.5 hours post-dose at Visit 2 (Week 0) and Visit 4 (Week 6).

Results are shown by treatment group, as change from baseline (in mmHg) for representative timepoints.

Definitions:

Baseline=Values recorded pre-dose (Visit 2, Week 0); Day 1=Day of the first dose of randomized study drug (Visit 2, Week 0);
Baseline, Day 1, Week 6
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
Time Frame: Baseline, Day 1, Week 6

Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Heart rate (HR)

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5m, +55m, and at +2.5 h.
Baseline, Day 1, Week 6
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
Time Frame: Baseline, Day 1, Week 6

Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - PR Interval

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Baseline, Day 1, Week 6
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
Time Frame: Baseline, Day 1, Week 6

Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - QRS Interval

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Baseline, Day 1, Week 6
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
Time Frame: Baseline, Day 1, Week 6

Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Fridericia-corrected QT interval (QTcF).

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Baseline, Day 1, Week 6
24-hour Holter ECG - Prolonged QTcF - Male Subjects
Time Frame: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Male subjects.

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Baseline, Day 1, Week 6
24-hour Holter ECG - Prolonged QTcF - Female Subjects
Time Frame: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Female subjects.

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Baseline, Day 1, Week 6
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
Time Frame: Baseline, Day 1, Week 6

24-hour Holter ECG - Prolonged QTcF - Change from baseline.

Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.

Results are presented as the number of subjects who had a change from baseline in QTcF of: > 30 msec, > 60 msec, and no prolongation (by > 30 msec or > 60 msec).
Baseline, Day 1, Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chiesi Farmaceutici S.p.A.

Investigators

  • Principal Investigator: Edward Kerwin, MD, Crisor LLC c/o Clinical Research Institute of Southern Oregon, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 28, 2017

Primary Completion (ACTUAL)

May 23, 2018

Study Completion (ACTUAL)

June 6, 2018

Study Registration Dates

First Submitted

March 8, 2017

First Submitted That Met QC Criteria

March 14, 2017

First Posted (ACTUAL)

March 21, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 15, 2021

Last Update Submitted That Met QC Criteria

May 20, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCD-05993AA3-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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