The Effects of RPL554 on Top of Standard COPD Reliever Medications

September 8, 2016 updated by: Verona Pharma plc

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.

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Salbutamol alone
200 micrograms salbutamol, ipratropium matched placebo and RPL554 matched placebo
Drug: Salbutamol
200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)
Drug: Ipratropium matched placebo
Placebo pMDI
Drug: RPL554 matched placebo
Nebulised placebo
Experimental: Salbutamol and RPL554
200 micrograms salbutamol, ipratropium matched placebo and 6 mg RPL554
Drug: Salbutamol
200 micrograms salbutamol administered using a pressurised metered dose inhaler (pMDI)
Drug: Ipratropium matched placebo
Placebo pMDI
Drug: RPL554
6 mg RPL554 administered using a nebuliser
Active Comparator: Ipratropium
Salbutamol matched placebo, 40 micrograms ipratropium and RPL554 matched placebo
Drug: RPL554 matched placebo
Nebulised placebo
Drug: Ipratropium
40 micrograms ipratropium administered using a pMDI
Drug: Salbutamol matched placebo
Placebo pMDI
Experimental: Ipratropium and RPL554
Salbutamol matched placebo, 40 micrograms ipratropium and 6 mg RPL554
Drug: RPL554
6 mg RPL554 administered using a nebuliser
Drug: Ipratropium
40 micrograms ipratropium administered using a pMDI
Drug: Salbutamol matched placebo
Placebo pMDI
Experimental: RPL554
Salbutamol matched placebo, ipratropium matched placebo and 6 mg RPL554
Drug: Ipratropium matched placebo
Placebo pMDI
Drug: RPL554
6 mg RPL554 administered using a nebuliser
Drug: Salbutamol matched placebo
Placebo pMDI
Placebo Comparator: Placebo
Salbutamol matched placebo, ipratropium matched placebo and RPL554 matched placebo
Drug: Ipratropium matched placebo
Placebo pMDI
Drug: RPL554 matched placebo
Nebulised placebo
Drug: Salbutamol matched placebo
Placebo pMDI

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
8 hour spirometry
Time Frame: 8 hours
Forced expired volume in one second (FEV1) over 8 hours post-dose
8 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
12 hour spirometry
Time Frame: 12 hours
FEV1 over 4, 6 and 12 hours post-dose
12 hours
Whole body plethysmography
Time Frame: 4 hours
Functional residual capacity, residual volume, total lung capacity, specific airway conductance, specific airway resistance at 1 and 4 hours post-dose
4 hours
Area under the curve (AUC)
Time Frame: 12 hours
AUC for RPL554 plasma concentration
12 hours
Maximum plasma concentration (Cmax)
Time Frame: 12 hours
Cmax for RPL554 plasma concentration
12 hours
Time to maximum plasma concentration (Tmax)
Time Frame: 12 hours
Tmax for RPL554 plasma concentration
12 hours
Adverse events
Time Frame: Up to 94 days
Continuous measurement of adverse events throughout the study
Up to 94 days
Safety laboratory tests
Time Frame: Up to 94 days
Laboratory safety tests at screening, before each treatment and end of study
Up to 94 days
ECG
Time Frame: Up to 94 days
12 lead ECG at screening, before and up to 12 hours after each treatment and end of study
Up to 94 days
Vital signs
Time Frame: Up to 94 days
Blood pressure and pulse rate at screening, before and up to 12 hours after each treatment and end of study
Up to 94 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Verona Pharma plc

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dave Singh, Medicines Evaluation Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 4, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 9, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RPL554-009-2015
  • 2015-002536-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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