An 8-week Dose Ranging Study of CHF 718 pMDI in Asthmatic Subjects
NCT ID: NCT03084718
Last Updated: 2021-12-14
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
610 participants
INTERVENTIONAL
2017-07-28
2018-12-05
Brief Summary
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Detailed Description
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After a 2 week run-in period under rescue albuterol as needed and background inhaled corticosteroid (ICS), patients will be randomized to one of the 5 study treatment groups. After randomization, patients will be assessed after 4 and 8 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 asthma symptoms, peak expiratory flow, rescue and background medication use, and compliance with the study medication will be recorded via subject diary. Treatment-Emergent Adverse Events (TEAEs) will be assessed and recorded throughout the study. At screening and subsequent visits, patients will undergo physical and vital signs examinations, spirometry measurements, and 12-lead ECG. Routine hematology, blood chemistry, and pregnancy testing will be performed before enrollment and at end of study. 24-hr urine cortisol and creatinine will be assessed before and after the first dose and just before the last dose of study treatment.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
OTHER
QUADRUPLE
Study Groups
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Treatment A
CHF 718 pMDI 100 μg Total Daily Dose (TDD), Dose 1; CHF 718 pMDI 50 μg/actuation: 1 inhalation twice daily (BID);
CHF 718 pMDI
Dose Response: Test one of three different doses of CHF 718 pMDI
Treatment B
CHF 718 pMDI 400 μg Total Daily Dose (TDD) 400 μg, Dose 2; CHF 718 pMDI 100 μg/actuation: 2 inhalations BID;
CHF 718 pMDI
Dose Response: Test one of three different doses of CHF 718 pMDI
Treatment C
CHF 718 pMDI Total Daily Dose (TDD) 800 μg, Dose 3; CHF 718 pMDI 100 μg/actuation: 4 inhalations BID;
CHF 718 pMDI
Dose Response: Test one of three different doses of CHF 718 pMDI
Treatment D
Placebo Control, Placebo; CHF 718 pMDI matched Placebo: 4 inhalations BID;
Placebo pMDI
Placebo Control
Treatment E
Beclomethasone dipropionate (BDP) Hydrofluoroalkane (HFA), Total Daily Dose (TDD) 320 µg; QVAR® 80 μg/actuation: 2 inhalations BID;
Beclomethasone Dipropionate (BDP)
Active Control
Interventions
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CHF 718 pMDI
Dose Response: Test one of three different doses of CHF 718 pMDI
Placebo pMDI
Placebo Control
Beclomethasone Dipropionate (BDP)
Active Control
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* A diagnosis of asthma as defined in the Global Initiative for Asthma (GINA) Report, 2016, documented for at least 1 year prior to screening.
* Subjects with poorly controlled or uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire 7 © (ACQ-7) ≥1.5 (this criterion must be met at screening and at randomization visits).
* Subjects with a pre-bronchodilator Forced Expiratory Volume in the 1st Second (FEV1) ≥50% and \<85% of their predicted normal value, after appropriate washout from bronchodilators, at the screening and randomization visits.
* Subjects with a positive response to a reversibility test at screening (pre - post BD), within 1 year prior to or at screening defined as ΔFEV1≥12% and ≥200 mL over baseline within 30 minutes after inhaling 4 puffs of albuterol HFA 90µg/actuation.
* Use of inhaled corticosteroids (low/medium dose according to GINA Report 2016) with or without a long-acting bronchodilator (LABD) for 3 months (stable dose in the last 4 weeks) before screening visit (V).
* A cooperative attitude and ability to demonstrate correct use of the diary, peak flow meter, and pMDI inhalers.
* A basal morning (7-10 am) serum cortisol level between 7-28 µg/dL at screening visit (V1).
* A Body Mass Index (BMI): 18.5 ≤ BMI \<35 kg/m\^2.
Exclusion Criteria
* Subjects who suffer from chronic obstructive pulmonary disease (COPD) as defined by the GOLD Report 2017, or are suspected of having Asthma COPD Overlap Syndrome (ACOS) as defined in GINA Report, 2016.
* Inability to carry out pulmonary lung function testing, to comply with study procedures or with study drug intake.
* Current smokers or ex-smokers (tobacco, vapor cigarettes, marijuana) with a smoking history of \>10 pack-years or having stopped smoking one year or less prior to screening visit.
* History of life-threatening asthma, clinically significant uncontrolled disease or respiratory infection.
* An asthma exacerbation requiring oral corticosteroids within 3 months or hospitalization within 6 months prior to screening.
* Subjects with unresolved bacterial or viral respiratory tract, sinus or middle ear infection affecting asthma status within 2 weeks prior to screening.
* Subjects who received a vaccination within 2 weeks prior to screening or during the run-in.
* Subjects with oral candidiasis at screening or at randomization.
* Subjects with any clinically significant, uncontrolled condition
* 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 and randomization visits.
* Subjects with known intolerance/hypersensitivity or contra-indication to treatment with ß2-adrenergic receptor agonists, inhaled corticosteroids or propellant gases/excipients.
* Subjects with concomitant immunosuppressive therapy, use of oral or injected corticosteroids, anti-Immunoglobulin E (IgE), anti-Interleukin 5 (IL5), or other monoclonal or polyclonal antibodies within 12 weeks prior to screening.
* Use of potent cytochrome P450 3A4 inhibitors and inducers within 4 weeks prior to screening.
* 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.
18 Years
75 Years
ALL
No
Sponsors
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Chiesi Farmaceutici S.p.A.
INDUSTRY
Responsible Party
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Principal Investigators
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David Bernstein, MD
Role: PRINCIPAL_INVESTIGATOR
Bernstein Clinical Research Center, LLC
Locations
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Chiesi Investigational Site
Birmingham, Alabama, United States
Chiesi Investigational Site
Montgomery, Alabama, United States
Chiesi Investigational Site
Phoenix, Arizona, United States
Chiesi Investigational Site
Surprise, Arizona, United States
Chiesi Investigational Site
Tempe, Arizona, United States
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Little Rock, Arkansas, United States
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Anaheim, California, United States
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Encinitas, California, United States
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Escondido, California, United States
Chiesi Investigational Site
Fullerton, California, United States
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Huntington Beach, California, United States
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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North Hollywood, California, United States
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Rolling Hills Estates, California, United States
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Sacramento, California, United States
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San Diego, California, United States
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San Diego, California, United States
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San Jose, 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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Colorado Springs, Colorado, United States
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Denver, Colorado, United States
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Greenwood, Colorado, United States
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Wheat Ridge, Colorado, United States
Chiesi Investigational Site
Aventura, Florida, United States
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Clearwater, Florida, United States
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Daytona Beach, Florida, United States
Chiesi Investigational Site
Doral, Florida, United States
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Gainesville, Florida, United States
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Hialeah, Florida, United States
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Kissimmee, Florida, United States
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Lauderdale Lakes, Florida, United States
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Loxahatchee Groves, Florida, United States
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Maitland, Florida, United States
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Miami, Florida, United States
Chiesi Investigational Site
Miami, Florida, United States
Chiesi Investigational Site
Miami, Florida, United States
Chiesi Investigational Site
Miami, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Palmetto Bay, Florida, United States
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Plantation, Florida, United States
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Pompano Beach, Florida, United States
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Saint Cloud, Florida, United States
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Sarasota, Florida, United States
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Winter Park, Florida, United States
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Dacula, Georgia, United States
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Duluth, Georgia, United States
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Gainesville, 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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Chicago, Illinois, United States
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Crowley, Louisiana, United States
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New Orleans, Louisiana, United States
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Baltimore, Maryland, United States
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Bethesda, Maryland, United States
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Fall River, Massachusetts, United States
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Fall River, Massachusetts, United States
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North Dartmouth, Massachusetts, United States
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South Dartmouth, Massachusetts, United States
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Detroit, Michigan, United States
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Minneapolis, Minnesota, United States
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Columbia, Missouri, United States
Chiesi Investigational Site
Festus, Missouri, United States
Chiesi Investigational Site
Rolla, Missouri, United States
Chiesi Investigational Site
St Louis, Missouri, United States
Chiesi Investigational Site
St Louis, Missouri, United States
Chiesi Investigational Site
Warrensburg, Missouri, United States
Chiesi Investigational Site
Missoula, Montana, United States
Chiesi Investigational Site
Omaha, Nebraska, United States
Chiesi Investigational Site
Las Vegas, Nevada, United States
Chiesi Investigational Site
Las Vegas, Nevada, United States
Chiesi Investigational Site
Skillman, New Jersey, United States
Chiesi Investigational Site
Albuquerque, New Mexico, United States
Chiesi Investigational Site
Albuquerque, New Mexico, United States
Chiesi Investigational Site
Brooklyn, New York, United States
Chiesi Investigational Site
New York, New York, United States
Chiesi Investigational Site
New York, New York, United States
Chiesi Investigational Site
The Bronx, New York, United States
Chiesi Investigational Site
Charlotte, North Carolina, United States
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
Chiesi Investigational Site
Hickory, North Carolina, United States
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Monroe, North Carolina, United States
Chiesi Investigational Site
Mooresville, North Carolina, United States
Chiesi Investigational Site
Winston-Salem, North Carolina, United States
Chiesi Investigational Site
Cincinnati, Ohio, United States
Chiesi Investigational Site
Cincinnati, Ohio, United States
Chiesi Investigational Site
Dayton, Ohio, United States
Chiesi Investigational Site
Dayton, Ohio, United States
Chiesi Investigational Site
Grove City, Ohio, United States
Chiesi Investigational Site
Munroe Falls, Ohio, United States
Chiesi Investigational Site
Toledo, Ohio, United States
Chiesi Investigational Site
Edmond, Oklahoma, United States
Chiesi Investigational Site
Medford, Oregon, United States
Chiesi Investigational Site
Portland, Oregon, United States
Chiesi Investigational Site
East Providence, Rhode Island, United States
Chiesi Investigational Site
East Providence, Rhode Island, United States
Chiesi Investigational Site
Warwick, Rhode Island, United States
Chiesi Investigational Site
Anderson, South Carolina, United States
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Gaffney, South Carolina, United States
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Greenville, South Carolina, United States
Chiesi Investigational Site
Rock Hill, South Carolina, United States
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Spartanburg, South Carolina, United States
Chiesi Investigational Site
Spartanburg, South Carolina, United States
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Union, South Carolina, United States
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Chattanooga, Tennessee, United States
Chiesi Investigational Site
Chattanooga, Tennessee, United States
Chiesi Investigational Site
Knoxville, Tennessee, United States
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Smyrna, Tennessee, United States
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Spring Hill, Tennessee, United States
Chiesi Investigational Site
Allen, Texas, United States
Chiesi Investigational Site
Beaumont, Texas, United States
Chiesi Investigational Site
Cypress, Texas, United States
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Dallas, Texas, United States
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Dallas, Texas, United States
Chiesi Investigational Site
El Paso, Texas, United States
Chiesi Investigational Site
McKinney, Texas, United States
Chiesi Investigational Site
Pearland, Texas, United States
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Plano, Texas, United States
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San Antonio, Texas, United States
Chiesi Investigational Site
Sherman, Texas, United States
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St. George, Utah, United States
Chiesi Investigational Site
South Burlington, Vermont, United States
Chiesi Investigational Site
Norfolk, Virginia, United States
Chiesi Investigational Site
Everett, Washington, United States
Chiesi Investigational Site
Greenfield, Wisconsin, United States
Countries
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References
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017.
COPD Foundation - What is COPD
Global Initiative For Asthma - GINA Report 2016
Centers for Disease Control and Prevention - Most Recent Asthma Data
Chiesi Farmaceutici S.p.A. - Respiratory
Chiesi Farmaceutici S.p.A - Press Release: Chiesi Farmaceutifici is the first company to submit a marketing authorisation application to the European Medicine Agency for a triple combination for the treatment of COPD
Wikipedia entry - Beclomethasone dipropionate
WebMD LLC - Serum Cortisol
Quest Diagnostics- Cortisol, Free and Cortisone, 24 Hour Urine with Creatinine
Other Identifiers
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CCD-05993AA3-01
Identifier Type: -
Identifier Source: org_study_id