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Comparison of RPL554 With Placebo and Salbutamol in Asthmatic Patients

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ClinicalTrials.gov Identifier: NCT02427165
Recruitment Status : Completed
First Posted : April 27, 2015
Last Update Posted : September 9, 2016
Sponsor:
Information provided by (Responsible Party):
Verona Pharma plc

Brief Summary:
The number of people with of asthma and allergy is still increasing and a large number of patients still do not have their asthma well controlled. There is therefore a need for new asthma treatments that work well and have less side effects. The study compares a new experimental drug RPL554 with a marketed asthma drug (salbutamol) and placebo.

Condition or disease Intervention/treatment Phase
Asthma Drug: RPL554 Drug: Salbutamol Drug: Placebo Phase 2

Detailed Description:

A seven way crossover study to investigate the pharmacodynamics, pharmacokinetics, safety and tolerability of inhaled RPL554 compared to salbutamol and placebo in patients with mild to moderate chronic asthma.

Salbutamol is a marketed beta-2 agonist typically used to treat bronchospasm (due to any cause, allergen asthma or exercise-induced), as well as chronic obstructive pulmonary disease but has associated dose-related systemic side effects.

RPL554 is a dual PDE3 and PDE4 inhibitor that has bronchodilatory and anti-inflammatory actions and also the potential to stimulate increases in mucociliary clearance via its proven ability to activate CFTR. Four different doses of RPL554 will be compared with placebo and a two doses of salbutamol as benchmarks for bronchodilation and systemic side effects.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Randomised, Double Blind, Placebo Controlled, Seven Way Crossover Study to Assess the Effect of Single Doses of RPL554 Compared to Salbutamol and Placebo Administered by Nebuliser on Lung Function of Patients With Chronic Asthma
Study Start Date : April 2015
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Placebo Comparator: Placebo
Single dose of nebulised placebo solution
Drug: Placebo
RPL554 placebo containing no active ingredients

Experimental: RPL554 Dose 1
0.4 mg single dose nebulised RPL554
Drug: RPL554
A dual PDE3 and PDE4 inhibitor
Other Names:
  • VMX554
  • VRP554

Experimental: RPL554 Dose 2
1.5 mg single dose nebulised RPL554
Drug: RPL554
A dual PDE3 and PDE4 inhibitor
Other Names:
  • VMX554
  • VRP554

Experimental: RPL554 Dose 3
6 mg single dose nebulised RPL554
Drug: RPL554
A dual PDE3 and PDE4 inhibitor
Other Names:
  • VMX554
  • VRP554

Experimental: RPL554 Dose 4
24 mg single dose nebulised RPL554
Drug: RPL554
A dual PDE3 and PDE4 inhibitor
Other Names:
  • VMX554
  • VRP554

Active Comparator: Salbutamol Dose 1
2.5 mg single dose nebulised salbutamol
Drug: Salbutamol
a beta-2 receptor agonist

Active Comparator: Salbutamol Dose 2
7.5 mg single dose nebulised salbutamol
Drug: Salbutamol
a beta-2 receptor agonist




Primary Outcome Measures :
  1. Spirometry [ Time Frame: 12 hours ]
    FEV1


Secondary Outcome Measures :
  1. Spirometry [ Time Frame: 4, 6 and 8 hours ]
    FEV1

  2. Systemic pharmacodynamic effect on blood pressure [ Time Frame: 4 hours ]
    Supine blood pressure in the 4 hours after nebulisation

  3. Systemic pharmacodynamic effect on pulse rate [ Time Frame: 4 hours ]
    Supine Pulse rate in the 4 hours after nebulisation

  4. Systemic pharmacodynamic effect on ECG heart rate [ Time Frame: 4 hours ]
    ECG heart rate in the 4 hours after nebulisation

  5. Vital signs (Supine pulse rate) [ Time Frame: 12 hours ]
    Supine pulse rate

  6. Vital signs (Supine blood pressure) [ Time Frame: 12 hours ]
    Supine systolic and diastolic blood pressure

  7. ECG [ Time Frame: 12 hours ]
    12-lead ECG parameters

  8. Pharmacokinetics (AUC) [ Time Frame: 12 hours ]
    RPL554 AUC

  9. Pharmacokinetics (Cmax) [ Time Frame: 12 hours ]
    RPL554 Cmax

  10. Pharmacokinetics (tmax) [ Time Frame: 12 hours ]
    RPL554 tmax

  11. Pharmacokinetics (half life) [ Time Frame: 12 hours ]
    RPL554 half life

  12. Pharmacokinetics (MRT) [ Time Frame: 12 hours ]
    RPL554 MRT



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provided written informed consent
  • Males agree not to donate sperm and either be abstinent or use adequate contraception. Females to be post-menopausal or surgically sterile
  • Non-smoker or ex-smoker >6 months
  • Diagnosed asthma for at least 6 months
  • Pre-bronchodilator FEV1 ≥60% and ≤90% of predicted normal value and ≥1.5 L at screening
  • Increase in FEV1 of 15% within 30 minutes after a 2.5mg dose of nebulised salbutamol
  • Systolic blood pressure 90 to 145 mmHg, diastolic blood pressure 50 to 90 mmHg and heart rate 45 to 80 beats per minute (bpm) after resting for 5 minutes in a supine position (average from two measurements)
  • Capable of withdrawing from LABAs, LAMAs and SAMAs before screening and during study and SABAs before screening and for 8 hours before each dose

Exclusion Criteria:

  • Asthma exacerbation in the last 3 months
  • Any prior life threatening episode of asthma (intensive care admission)
  • Any clinically significant disease or disorder or clinically relevant screening result
  • QTcF interval >450 ms or QT interval >500 ms or other abnormality in ECG
  • History of ischemic heart disease or heart failure. History of recurrent or current clinically significant arrhythmia or ECG abnormality as judged by the investigator
  • Treatment with systemic glucocorticosteroids within 30 days before screening
  • A suspected/manifested infection according to WHO risk classification 2, 3 or 4

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427165


Locations
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Sweden
Skane University Hospital
Lund, Sweden
United Kingdom
Celerion
Belfast, United Kingdom
Sponsors and Collaborators
Verona Pharma plc
Investigators
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Principal Investigator: Lief Bjermer Skane University Hospital, Sweden
Principal Investigator: Johnston Stewart Celerion, Northern Ireland

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Verona Pharma plc
ClinicalTrials.gov Identifier: NCT02427165     History of Changes
Other Study ID Numbers: RPL554-008-2014
First Posted: April 27, 2015    Key Record Dates
Last Update Posted: September 9, 2016
Last Verified: September 2016
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action