The Effects of RPL554 on Top of Standard COPD Reliever Medications

NCT ID: NCT02542254

Last Updated: 2016-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2015-12-31

Brief 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

Detailed Description

The purpose of this study is to investigate if RPL554 has an additive bronchodilator effect when administered in combination with standard of care bronchodilators in patients with COPD.This study investigates the pharmacodynamic effect of RPL554 using spirometry and whole body plethysmography compared to placebo, when administered in addition to a beta2 agonist (salbutamol), a muscarinic antagonist (ipratropium) or placebo.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Salbutamol alone

200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo

Group Type: ACTIVE_COMPARATOR

Salbutamol

Intervention Type: DRUG

200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)

Ipratropium matched placebo

Intervention Type: DRUG

Placebo pMDI

RPL554 matched placebo

Intervention Type: DRUG

Nebulised placebo

Salbutamol and RPL554

200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554

Group Type: EXPERIMENTAL

Salbutamol

Intervention Type: DRUG

200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)

RPL554

Intervention Type: DRUG

6 mg RPL554 administered using a nebuliser

Ipratropium matched placebo

Intervention Type: DRUG

Placebo pMDI

Ipratropium

Salbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo

Group Type: ACTIVE_COMPARATOR

Ipratropium

Intervention Type: DRUG

40 micrograms ipratropium administered using a pMDI

Salbutamol matched placebo

Intervention Type: DRUG

Placebo pMDI

RPL554 matched placebo

Intervention Type: DRUG

Nebulised placebo

Ipratropium and RPL554

Salbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554

Group Type: EXPERIMENTAL

Ipratropium

Intervention Type: DRUG

40 micrograms ipratropium administered using a pMDI

RPL554

Intervention Type: DRUG

6 mg RPL554 administered using a nebuliser

Salbutamol matched placebo

Intervention Type: DRUG

Placebo pMDI

RPL554

Salbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554

Group Type: EXPERIMENTAL

RPL554

Intervention Type: DRUG

6 mg RPL554 administered using a nebuliser

Salbutamol matched placebo

Intervention Type: DRUG

Placebo pMDI

Ipratropium matched placebo

Intervention Type: DRUG

Placebo pMDI

Placebo

Salbutamol matched placebo, ipratropium matched placebo and RPL554 matched placebo

Group Type: PLACEBO_COMPARATOR

Salbutamol matched placebo

Intervention Type: DRUG

Placebo pMDI

Ipratropium matched placebo

Intervention Type: DRUG

Placebo pMDI

RPL554 matched placebo

Intervention Type: DRUG

Nebulised placebo

Interventions

Salbutamol

200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)

Intervention Type: DRUG

Ipratropium

40 micrograms ipratropium administered using a pMDI

Intervention Type: DRUG

RPL554

6 mg RPL554 administered using a nebuliser

Intervention Type: DRUG

Salbutamol matched placebo

Placebo pMDI

Intervention Type: DRUG

Ipratropium matched placebo

Placebo pMDI

Intervention Type: DRUG

RPL554 matched placebo

Nebulised placebo

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Verona Pharma plc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dave Singh

Role: PRINCIPAL_INVESTIGATOR

Medicines Evaluation Unit

Locations

Medicines Evaluation Unit

Manchester, , United Kingdom

Countries

United Kingdom

References

Singh D, Abbott-Banner K, Bengtsson T, Newman K. The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD. Eur Respir J. 2018 Nov 1;52(5):1801074. doi: 10.1183/13993003.01074-2018. Print 2018 Nov.

Reference Type: DERIVED

PMID: 30166326 (View on PubMed)

Other Identifiers

2015-002536-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RPL554-009-2015

Identifier Type: -

Identifier Source: org_study_id