The Effects of RPL554 on Top of Standard COPD Reliever Medications

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease Read More

Inclusion Criteria:

• Provide informed consent
• Males not donating sperm and using adequate contraception or females who are surgically sterile or postmenopausal
• 12-lead ECG showing:Heart rate 45 to 90 bpm, QTcF≤450 msec, QRS ≤120 msec, PR interval ≤220 msec, no clinically significant abnormality
• Capable of complying with all study restrictions and procedures including ability to use the study nebuliser correctly.
• BMI 18 to 33 kg/m2 with a minimum weight of 45 kg.
• COPD diagnosis for at least 1 year and clinically stable COPD in previous 4 weeks

• Demonstrates reversibility to bronchodilator (two puffs of salbutamol followed by two puffs of ipratropium) via spirometry:

  • Post-bronchodilator FEV1/forced vital capacity (FVC) ratio of ≤0.70
  • Post-bronchodilator FEV1 ≥40 % and ≤80% of predicted normal
  • ≥150 mL increase from pre-bronchodilator FEV1
• Chest X-ray showing no abnormalities
• Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
• Smoking history of ≥10 pack years.
• Capable of withdrawing from long acting bronchodilators throughout the study and short acting bronchodilators for 8 hours prior to study treatment.

Exclusion Criteria:

• History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
• COPD exacerbation requiring oral steroids in the previous 3 months
• History of one or more hospitalisations for COPD in the previous 12 months
• Respiratory tract infection (both upper and lower) treated with antibiotics in previous 12 weeks
• Evidence of cor pulmonale or clinically significant pulmonary hypertension.
• Other respiratory disorders
• Previous lung resection or lung reduction surgery.
• Oral therapies for COPD in the previous 3 months and throughout the study.
• Drug or alcohol abuse in the past 3 years
• Received an experimental drug within 3 months or five half lives, whichever is longer.
• Prior exposure to RPL554
• Patients with a history of chronic uncontrolled disease that the Investigator believes are clinically significant.
• Documented cardiovascular disease in last 3 months
• Major surgery, (requiring general anaesthesia) in the previous 6 weeks, or will not have fully recovered from surgery, or planned surgery through the end of the study.
• History of malignancy of any organ system within 5 years with the exception of localised skin cancers (basal or squamous cell)
• Clinically significant abnormal values for safety laboratory tests
• A disclosed history, or one known to the Investigator, of significant non compliance in previous investigational studies or with prescribed medications.
• Requires oxygen therapy, even on an occasional basis.
• Inability to adequately perform whole body plethysmography.
• Any other reason that the Investigator considers makes the subject unsuitable to participate.
• Patients with known hypersensitivity to atropine or its derivatives, or to ipratropium bromide, salbutamol or RPL554 or their excipients/components.