Patients with chronic asthma MedDRA version: 17.1 Level: LLT Classification code 10049106 Term: Asthma chronic System Organ Class: 100000004855
Conditions
Interventions
Product Name: RPL554
Product Code: RPL554
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: RPL554
CAS Number: 298680-25-8
Current Sponsor code: RPL554
Concentration unit: mg/ml milligram
Sponsors
Verona Pharma plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent prior to any study specific procedures 2. Males or females aged 18 to 65 years (inclusive) 3. a) Males must be willing, able and agree to meet the following from the first dose up to 30 days after the last dose of study drug: - Not donate sperm - Either: be sexually abstinent in accordance with a patient’s usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change) Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second reliable form of contraception must also be used (e.g. diaphragm/cap with spermicide, established hormonal contraception, intra-uterine device) b) Females must be either post-menopausal (defined as amenorrheic for 12 months and follicle stimulating hormone plasma concentration within the post-menopausal range as defined by the laboratory) or surgically sterile (hysterectomy, tubal ligation, hysteroscopic sterilisation) 4. Body mass index (BMI) between 18 and 30 kg/m2 (inclusive) 5. Non-smoker or ex-smoker who has stopped smoking for >6 months before screening and have a smoking history of not more than 10 pack years 6. Diagnosed asthma for at least 6 months. Asthma is defined according to the global initiative for asthma (GINA), 2012 7. Pre-bronchodilator FEV1 =60% and =90% of predicted normal value and =1.5 L at screening 8. Increase in FEV1 of =15% within 30 minutes after a 2.5mg dose of nebulised salbutamol 9. Able to correctly use the study nebuliser 10. Able to complete the clinical study 11. 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) 12. Patients must be capable of withdrawing from long acting ß2 agonists (LABAs) and long acting muscarinic antagonists (LAMAs) for 72 hours and short acting muscarinic antagonists (SAMAs) for 8 hours before the reversibility test at screening and expected to be able to withhold during study 13. Patients must be capable of withdrawing from short acting ß2 agonists (SABAs) for 8 hours before the reversibility test at screening and 8 hours before all study drug administrations Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Asthma exacerbation (defined as requiring medical intervention) in the 3 months before screening 2. Any prior life threatening episode of asthma (intensive care admission) 3. Any clinically significant disease or disorder (e.g. cardiovascular, pulmonary other than asthma, chronic obstructive pulmonary disease [COPD], gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the result of the study, or the patient´s ability to participate in the study 4. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, ECG or lung function at screening, which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study 5. QTcF interval >450 ms or QT interval >500 ms or other abnormality in ECG making interpretation more difficult, as judged by the Investigator 6. History of ischemic heart disease or heart failure. History of recurrent or current clinically significant arrhythmia or ECG abnormality as judged by the investigator 7. Treatment with systemic glucocorticosteroids within 30 days before screening 8. A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the Investigator 9. Donation of blood within 1 month or donation of plasma within 14 days before screening 10. History of, or current alcohol or drug abuse, as judged by the Investigator 11. A suspected/manifested infection according to the World Health Organisation (WHO) risk classification 2, 3 or 4 12. Positive results on screening tests for hepatitis B and/or C and/or human immunodeficiency virus (HIV) 13. Previous randomisation to treatment in the present study 14. Participation in another investigational medicinal product study within 3 months or five half-lives (whichever is longer) before screening 15. Planned in-patient surgery, dental procedure or hospitalisation during the study 16. Patients who, in the opinion of the Investigator, should not participate in the study 17. Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study centre, or their relatives in both cases)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the bronchodilator effect of single doses of RPL554 administered by nebuliser on peak and average* FEV1 over 12 hours compared with placebo and salbutamol. *The average effect will be calculated as the area under the curve divided by the length of the time interval of interest, and the peak effect as the minimum value for diastolic blood pressure or maximum value for other variables;Secondary Objective: • To investigate the bronchodilator effect of single doses of RPL554 administered by nebuliser on peak and average* FEV1 over 4, 6 and 8 hours compared with placebo and salbutamol • To investigate the pharmacodynamic effect of single doses of RPL554 administered by nebuliser on peak and average* blood pressure, pulse rate and ECG heart rate over 4 hours compared with placebo and salbutamol • To analyse plasma concentrations and assess the pharmacokinetics of RPL 554 • To assess the tolerability and safety of single doses of RPL554 administered by nebuliser compared with placebo and salbutamol *The average effect will be calculated as the area under the curve divided by the length of the time interval of interest, and the peak effect as the minimum value for diastolic blood pressure or maximum value for other variables;Primary end point(s): Peak and average FEV1 following start of nebulisation;Timepoint(s) of evaluation of this end point: 12 hours | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Average FEV1 following start of nebulisation and onset of action • Peak and average blood pressure and pulse rate and ECG heart rate following start of nebulisation (pharmacodynamics) • RPL554 pharmacokinetics (area under the curve [AUC], maximum concentration of RPL554 in blood [Cmax], time to maximum concentration [tmax,] half life of RPL554 [t1/2], mean residence time [MRT]) • Safety and tolerability: o Continuous monitoring of AEs o Laboratory safety tests [haematology, biochemistry and urinalysis] pre-dose and post dose with further post-dose measurements of glucose and potassium only o 12-lead ECG, supine vital signs;Timepoint(s) of evaluation of this end point: • Average FEV1 over 4, 6 and 8 hours following start of nebulisation and onset of action • Peak and average blood pressure and pulse rate and ECG heart rate over 4 hours following start of nebulisation (pharmacodynamics) • RPL554 pharmacokinetics (area under the curve [AUC], maximum concentration of RPL554 in blood [Cmax], time to maximum concentration [tmax,] half life of RPL554 [t1/2], mean residence time [MRT]) from a 12 hour profile • Safety and tolerability: o Continuous monitoring of AEs o Laboratory safety tests [haematology, biochemistry and urinalysis] pre-dose and 12 hours post-dose with further post-dose measurements of glucose and potassium only over 2 hours o 12-lead ECG, supine vital signs over 12 hours | — |
Countries
Sweden, United Kingdom
Contacts
Public ContactSenior Scientist, Development
Verona Pharma plc
Outcome results
None listed