Status:
COMPLETED
Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients
Lead Sponsor:
Verona Pharma plc
Conditions:
COPD
Eligibility:
All Genders
40-75 years
Phase:
PHASE2
Brief Summary
The study investigates the effect of 4 weeks of twice daily treatment of four different doses of RPL554 (a phosphodiesterase \[PDE\]3/4 inhibitor) or placebo in patients with moderate to severe chroni...
Detailed Description
RPL554 is a dual inhibitor of PDE3 and PDE4 which are known to have a role in modulating the inflammatory airway response in respiratory diseases, including COPD. PDE3 inhibitors act as bronchodilator...
Eligibility Criteria
Inclusion
- Provide informed consent
- Male or female aged 40 to 75 years
- Meeting specified contraception requirements
- 12-lead electrocardiogram with heart rate 50-90 beats per minute, QT interval corrected using Fridericia's formula (QTcF) ≤450 msec (males) or ≤470 msec (females), QRS interval ≤120 msec, PR interval ≤200 msec and no clinically significant abnormalities
- Capable of complying with all study restrictions and procedures, including ability to use the study nebulizer correctly.
- Body mass index (BMI) 18 to 35 kg/m2 and minimum weight 45 kg.
- COPD diagnosis with symptoms compatible with COPD for at least 1 year
- Clinically stable COPD in the previous 4 weeks
- Ability to perform acceptable and reproducible spirometry.
- Post-bronchodilator spirometry at screening must demonstrate FEV1/forced vital capacity (FVC) ratio of ≤0.70 and FEV1 must be ≥40 % to ≤80% of predicted normal
- Chest X-ray (posterior-anterior) at screening, or chest X-ray, magnetic resonance imaging (MRI) or computed tomography (CT) scan in the last 12 months, showing no abnormalities which are both clinically significant and 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 a smoking history of ≥10 pack years.
- Capable of withdrawing long acting bronchodilators until the end of the treatment period, and short acting bronchodilators for 8 hours prior to administration of study medication.
Exclusion
- A history of life-threatening COPD including Intensive Care Unit admission and requiring intubation.
- COPD exacerbation requiring oral steroids in the previous 3 months
- A history of one or more hospitalizations for COPD in the previous 6 months
- Lower respiratory tract infection treated with antibiotics in the previous 3 months
- Evidence of cor pulmonale or clinically significant pulmonary hypertension.
- Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea, known alpha-1 antitrypsin deficiency or other active pulmonary diseases.
- Previous lung resection or lung reduction surgery.
- Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) in the previous 3 months and throughout the study.
- Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Visit 1) and remains stable during the trial.
- A history of, or reason to believe a subject has, drug or alcohol abuse in the previous 3 years.
- Received an experimental drug within 30 days or five half-lives of the first dose
- Prior exposure to RPL554.
- Women who are pregnant or breast-feeding.
- Patients with a history of current uncontrolled disease that the Investigator believes are clinically significant.
- myocardial infarction in the previous 6 month; congestive heart failure, a history of unstable or uncontrolled hypertension, or has been diagnosed with hypertension in last 3 months.
- Use of oral beta blockers.
- Major surgery (requiring general anesthesia) in the previous 6 weeks, lack of full recovery from surgery at screening, or planned surgery through the end of the study.
- 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 safety laboratory tests
- Significant non-compliance in previous investigational studies or with prescribed medications.
- Requirement for oxygen therapy, even on an occasional basis.
- Known hypersensitivity to RPL554 or its excipients/components.
- Abnormal clinically significant 12 lead Holter findings,
- Any other reason that the Investigator considers makes the subject unsuitable to participate.
Key Trial Info
Start Date :
June 1 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 7 2018
Estimated Enrollment :
405 Patients enrolled
Trial Details
Trial ID
NCT03443414
Start Date
June 1 2017
End Date
February 7 2018
Last Update
June 4 2019
Active Locations (49)
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