Study Investigating the Effect of 4 Doses of RPL554 Given in Addition to Tiotropium to Patients With COPD
NCT ID: NCT03937479
Last Updated: 2020-11-20
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
416 participants
INTERVENTIONAL
2019-05-01
2019-11-15
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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RPL554 0.375 mg twice daily
RPL554 0.375 mg twice daily
Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.375 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
RPL554 0.75 mg twice daily
RPL554 0.75 mg twice daily
Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.75 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
RPL554 1.5 mg twice daily
RPL554 1.5 mg twice daily
Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 1.5 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
RPL554 3.0 mg twice daily
RPL554 3.0 mg twice daily
Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 3.0 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Placebo twice daily
Placebo twice daily
Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● Placebo twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Interventions
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Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.375 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.75 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 1.5 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 3.0 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● Placebo twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Eligibility Criteria
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Inclusion Criteria
* Male or female aged between 40 and 80 years inclusive, at the time of informed consent.
* Must agree to meet the following from the first dose up to 1 month after the last dose of study medication:
* If male:
* Not donate sperm
* Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change)
* Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second reliable form of contraception must also be used (e.g., diaphragm/cap with spermicide, established hormonal contraception, intra-uterine device)
* If female:
* be of non-childbearing potential or use a highly effective form of contraception
* Have a 12-lead ECG recording at Screening showing the following (and no changes in the pre-dose value at the first treatment deemed clinically significant by the Investigator):
* Heart rate between 45 and 90 beats per minute
* QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males, and ≤ 470 msec for females
* QRS interval ≤ 120 msec
* No clinically significant abnormality including morphology (e.g., left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities consistent with ischemia)
* Capable of complying with study restrictions and procedures, including ability to use the nebulizer correctly.
* Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
* COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to Screening.
* Ability to perform acceptable and reproducible spirometry.
* Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
* FEV1/ FVC ratio of ≤0.70
* FEV1 ≥30% and ≤70% of predicted normal\* \*National Health and Nutrition Examination Survey (NHANES) III (Hankinson et al, 1999) will be used as the reference for normal predicted values.
* Clinically stable COPD in the 4 weeks prior to Screening (Visit 1) and during the period between Visits 1 and 2.
* A score of ≥2 on the modified Medical Research Council (mMRC) dyspnea scale at Screening.
* A chest X-ray (posterior-anterior) at Screening, or in the 12 months prior to Screening showing no clinically significant abnormalities unrelated to COPD.
* Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
* Current and former smokers with smoking history of ≥10 pack years.
* Capable of withdrawing from long acting bronchodilators (other than tiotropium) for the duration of the study, and short acting bronchodilators for 6 hours prior to dosing.
Exclusion Criteria
* COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to the first treatment.
* A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to the first treatment.
* Intolerance or hypersensitivity to albuterol, tiotropium or other muscarinic receptor antagonists.
* Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, uncontrolled or unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension or other active pulmonary diseases.
* Previous lung resection or lung reduction surgery.
* Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
* Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) or antibiotics within 3 months prior to Screening, or ICS therapy within 4 weeks prior to Screening
* Prior exposure to RPL554.
* History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
* Received an experimental drug within 30 days or five half-lives, whichever is longer.
* Women who are pregnant or breast-feeding.
* Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant. This includes any hepatic disease or moderate to severe renal impairment.
* Documented clinically significant cardiovascular disease such as: any history of arrhythmias, angina, recent (\<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening.
* Use of non-selective oral β-blockers.
* Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
* Required use of oxygen therapy, even on an occasional basis.
* History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell).
* Clinically significant abnormal values for laboratory safety tests (hematology, blood chemistry, viral serology or urinalysis) at Screening, as determined by the Investigator. In particular, alanine aminotransferase or aspartate aminotransferase cannot be more than twice the upper limit of normal.
* Patients with conditions which are sensitive to antimuscarinic effects such as narrow angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction.
* Current marijuana use (all forms).
* A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
* Any other reason that the Investigator considers makes the patient unsuitable to participate.
40 Years
80 Years
ALL
No
Sponsors
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Iqvia Pty Ltd
INDUSTRY
LGC Limited
INDUSTRY
Verona Pharma plc
INDUSTRY
Responsible Party
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Principal Investigators
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Gary Ferguson
Role: PRINCIPAL_INVESTIGATOR
Pulmonary Research Institute of Southeast Michigan
Locations
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Pinnacle Research Group, LLC
Anniston, Alabama, United States
California Research Medical Group, Inc
Fullerton, California, United States
Southern California Institute For Respiratory Diseases, Inc.
Los Angeles, California, United States
Innovative Clinical Research
Lafayette, Colorado, United States
Meris Clinical Research
Brandon, Florida, United States
Clinical Research of West Florida
Clearwater, Florida, United States
Pulmonary Disease Specialists, PA d/b/a PDS Research
Kissimmee, Florida, United States
Medical Research of Central Florida, LLC
Leesburg, Florida, United States
Clinical Trials of Florida, LLC
Miami, Florida, United States
Peninsula Research, Ormond Beach, LLC
Ormond Beach, Florida, United States
Medsol Clinical Research Center, Inc
Port Charlotte, Florida, United States
Progressive Medical Research
Port Orange, Florida, United States
Pasadena Center for Medical Research, LLC
St. Petersburg, Florida, United States
Florida Pulmonary Research Institute, LLC
Winter Park, Florida, United States
Columbus Regional Research Institute
Columbus, Georgia, United States
VitaLink Research - Hamilton Mill
Dacula, Georgia, United States
VitaLink Research - Duluth
Duluth, Georgia, United States
Gwinnett Biomedical Research
Lawrenceville, Georgia, United States
IACT Health
Rincon, Georgia, United States
Vitalink
Winder, Georgia, United States
Genesis Clinical Research and Consulting, LLC
Fall River, Massachusetts, United States
Pulmonary Research Institute of Southeast Michigan
Farmington Hills, Michigan, United States
Cities Research Center
Fridley, Minnesota, United States
American Health Research
Charlotte, North Carolina, United States
Clinical Research of Gastonia
Gastonia, North Carolina, United States
Research Carolina of Huntersville
Huntersville, North Carolina, United States
Clinical Research of Lake Norman
Mooresville, North Carolina, United States
New Horizons Clinical Research
Cincinnati, Ohio, United States
Aventiv Research, Inc
Columbus, Ohio, United States
Aventiv Research, Inc
Dublin, Ohio, United States
Crisor, LLC
Medford, Oregon, United States
Vitalink Research - Anderson
Anderson, South Carolina, United States
Lowcountry Lung and Critical Care, PA
Charleston, South Carolina, United States
VitaLink-Columbia
Columbia, South Carolina, United States
VitaLink Research - Easley
Easley, South Carolina, United States
Piedmont Research Partners, LLC
Fort Mill, South Carolina, United States
VitaLink Research-Gaffney
Gaffney, South Carolina, United States
VitaLink Research-Greenville
Greenville, South Carolina, United States
VitaLink Research-UPSTATE
Greenville, South Carolina, United States
Clinical Research of Charleston
Mt. Pleasant, South Carolina, United States
Clinical Research of Rock Hill
Rock Hill, South Carolina, United States
Vitalink Research-Seneca
Seneca, South Carolina, United States
Fusion Clinical Research of Spartanburg, LLC
Spartanburg, South Carolina, United States
Spartanburg Medical Research
Spartanburg, South Carolina, United States
Vitalink Research-Spartanburg
Spartanburg, South Carolina, United States
VitaLink Research - Union
Union, South Carolina, United States
New Phase Research & Development
Knoxville, Tennessee, United States
FMC Science, LLC
Lampasas, Texas, United States
DCOL Center for Clinical Research
Longview, Texas, United States
Metroplex Pulmonary and Sleep Center
McKinney, Texas, United States
Countries
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Provided Documents
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Document Type: Statistical Analysis Plan
Document Type: Study Protocol
Other Identifiers
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RPL554-CO-205
Identifier Type: -
Identifier Source: org_study_id