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)

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

Sponsors

Lead sponsor: Chiesi Farmaceutici S.p.A.

Source Chiesi Farmaceutici S.p.A.
Brief Summary

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.

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 with respect to lung function and other clinical efficacy and safety outcomes.

After a 2 week run-in period under rescue albuterol and background ICS as needed, patients will be randomized to one of the 6 study treatment groups. Following randomization, subjects will be assessed after 3 weeks and 6 weeks of study treatment at the center. A follow-up phone call will be performed a week after the last visit.

During the study, daily symptoms, rescue and background medication use and compliance with the study drug will be recorded via a subject diary. Treatment-Emergent Adverse Events (TEAEs) will be assessed and recorded throughout the study. At screening and subsequent visits, subjects will undergo physical and vital signs examinations, spirometry measurements, and 12-lead ECG. Symptoms and COPD health status will be assessed through validated questionnaires. Routine hematology, blood chemistry, and pregnancy testing will be performed before enrollment and at end of study. 24-hour digital recording of ECGs (Holter) will be performed before and after the first dose and just before the last dose of study treatment.

Overall Status Completed
Start Date July 28, 2017
Completion Date June 6, 2018
Primary Completion Date May 23, 2018
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from baseline in FEV1 AUC(0-12h) normalized by time at Week 6. 6 Weeks
Secondary Outcome
Measure Time Frame
Change from baseline in FEV1 AUC0-12h normalized by time at Day 1 6 Weeks
Change from baseline in FEV1 AUC0-4h normalized by time at Day 1 and Week 6 6 Weeks
Change from baseline in pre-dose morning FEV1 at Week 3 and Week 6 3 Weeks & 6 Weeks
Time to onset of action (change from baseline in post-dose FEV1 ≥ 100 mL) at Day 1 6 Weeks
TDI focal score at Week 3 and Week 6 6 Weeks
Change from baseline in %rescue medication-free days 6 Weeks
Change from baseline in average COPD symptom scores 6 Weeks
Adverse Events (AEs) and Adverse Drug Reactions (ADRs) 6 Weeks
Vital signs (systolic and diastolic blood pressure) 6 Weeks
24-hour digital Holter ECG parameters (HR, QTcF, QRS, PR) 6 Weeks
24-hour HR average, minimum and maximum 6 Weeks
24-hour digital Holter ECG abnormal findings 6 Weeks
Standard blood chemistry and hematology 6 Weeks
Enrollment 735
Condition
Intervention

Intervention type: Drug

Intervention name: CHF 5259

Description: Dose Response: Test one of four different doses of CHF 5259

Intervention type: Drug

Intervention name: Placebo

Description: Placebo Control

Arm group label: Treatment E

Intervention type: Drug

Intervention name: Tiotropium Bromide 18 MCG Inhalation Capsule

Description: Active Control

Arm group label: Treatment F

Other name: SPIRIVA® HANDIHALER®

Eligibility

Criteria:

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 FEV1 ≥50% and <80% of the predicted normal value and,

- a post-bronchodilator FEV1/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 LAMA, inhaled ICS/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 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.

Gender: All

Minimum age: 40 Years

Maximum age: N/A

Healthy volunteers: No

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

United States

Verification Date

May 2019

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Arm group label: Treatment A

Arm group type: Experimental

Description: CHF 5259 pMDI Dose 1

Arm group label: Treatment B

Arm group type: Experimental

Description: CHF 5259 pMDI Dose 2

Arm group label: Treatment C

Arm group type: Experimental

Description: CHF 5259 pMDI Dose 3

Arm group label: Treatment D

Arm group type: Experimental

Description: CHF 5259 pMDI Dose 4

Arm group label: Treatment E

Arm group type: Placebo Comparator

Description: Placebo Control

Arm group label: Treatment F

Arm group type: Active Comparator

Description: Tiotropium Bromide inhalation powder, 18 µg

Acronym GLIMMER
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Other

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov