The Effects of RPL554 on Top of Standard COPD Reliever Medications

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the addition of RPL554 to standard reliever medications for chronic obstructive pulmonary disorder (COPD). All patients will receive the same six treatments in a randomised sequence:

1. salbutamol,

2. ipratropium,

3. salbutamol + RPL554,

4. ipratropium + RPL554,

5. RPL554

6. Placebo

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

Details

• Lead Sponsor: Verona Pharma plc
• Treatments: Albuterol; Ipratropium

Criteria

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.