The Effects of RPL554 on Top of Standard COPD Reliever Medications

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Phase II, Randomised, Double Blind, Placebo Controlled, Six Way Crossover Study to Assess the Bronchodilator Effect of RPL554 Administered on Top of Salbutamol and Ipratropium in Patients With COPD.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02542254
• Other study ID #: RPL554-009-2015
• Secondary ID: 2015-002536-41
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2015
• Last updated: September 8, 2016
• Start date: October 2015
• Est. completion date: December 2015

Study information

• Verified date: September 2016
• Source: Verona Pharma plc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Salbutamol
200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)
• Ipratropium
40 micrograms ipratropium administered using a pMDI
• RPL554
6 mg RPL554 administered using a nebuliser
• Salbutamol matched placebo
Placebo pMDI
• Ipratropium matched placebo
Placebo pMDI
• RPL554 matched placebo
Nebulised placebo

Locations

Country	Name	City	State
United Kingdom	Medicines Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Verona Pharma plc

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	8 hour spirometry	Forced expired volume in one second (FEV1) over 8 hours post-dose	8 hours	No
Secondary	12 hour spirometry	FEV1 over 4, 6 and 12 hours post-dose	12 hours	No
Secondary	Whole body plethysmography	Functional residual capacity, residual volume, total lung capacity, specific airway conductance, specific airway resistance at 1 and 4 hours post-dose	4 hours	No
Secondary	Area under the curve (AUC)	AUC for RPL554 plasma concentration	12 hours	No
Secondary	Maximum plasma concentration (Cmax)	Cmax for RPL554 plasma concentration	12 hours	No
Secondary	Time to maximum plasma concentration (Tmax)	Tmax for RPL554 plasma concentration	12 hours	No
Secondary	Adverse events	Continuous measurement of adverse events throughout the study	Up to 94 days	Yes
Secondary	Safety laboratory tests	Laboratory safety tests at screening, before each treatment and end of study	Up to 94 days	Yes
Secondary	ECG	12 lead ECG at screening, before and up to 12 hours after each treatment and end of study	Up to 94 days	Yes
Secondary	Vital signs	Blood pressure and pulse rate at screening, before and up to 12 hours after each treatment and end of study	Up to 94 days	Yes