Study Investigating the Effect of 4 Doses of RPL554 Given in Addition to Tiotropium to Patients With COPD

Completed · Phase 2 · Has a placebo group

Conditions studied: COPD

In brief

The purpose of this study is to investigate the dose response of RPL554 in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE that are still symptomatic despite treatment with a stable background of tiotropium over 4 weeks of treatment. This study is intended to support optimal dose selection for a Phase III program evaluating RPL554 as an add-on treatment to standard of care therapy.

Key facts

Study ID

NCT03937479

Run by

Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA

People needed

416

Starts

2019-05-01

Expected to finish

2019-11-15

Last updated by the study team

2020-11-20

Who can join

Age: 40 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
• 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.

You may not qualify if…

• A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• 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.

Where it is running

• 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

Full record on ClinicalTrials.gov

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