Dose Ranging Study of RPL554 in Chronic Obstructive Pulmonary Disease (COPD) Patients

• Status: Completed
• Trial end date: 2018-02-07
• Target enrollment: 0
• Participant gender: All

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 chronic obstructive pulmonary disease (COPD). Patients will be equally allocated to one of the five treatment options.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Verona Pharma plc

Criteria

Inclusion Criteria:

• 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 Criteria:

• 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.