Allergic Asthma MedDRA version: 12.1 Level: LLT Classification code 10001705 Term: Allergic asthma
Conditions
Sponsors
Verona Pharma plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Males or females of non-child bearing potential: a) following hysterectomy or b) tubal ligation, or c) post-menopausal for at least 12 months before start of study •Age between 18 and 55 years at screening (both inclusive) •No clinically relevant history of cardiovascular (including arrhythmias) disease; no active hyperthyroidism •No clinically relevant history of chronic or malignant diseases (except for in situ basalioma) •Body mass index (BMI) between 18 and 33 kg/m2 (both inclusive) •Systolic blood pressure (SBP) 100-155 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and heart rate (HR) 45-90 beats per min (inclusive), measured on the arm with the highest blood pressure after resting for 5 min in the supine position •No clinically significant findings on physical examination other than allergy and mild to moderate persistent asthma •12-lead ECG without clinically relevant abnormalities •No recent respiratory tract infections (within 3 weeks of screening and during study) •Non-smokers or ex-smokers (stopped for at least 6 months before screening, and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Desensitization therapy in the past 5 years •Severe exacerbation requiring hospital evaluation and/or admission in the past 2 years •Unstable/uncontrolled disease within 3 weeks of participation in the study •History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug •Treatment with another investigational drug within 3 months prior to screening •Known hypersensitivity to any excipients of the drug formulations •History or clinical evidence of alcoholism within the 3-year period prior to screening (i.e. regular use of more than 21 units of alcohol/week for males and more than 14 units/week for females) •Excessive caffeine consumption, defined as > 8 cups/per day at screening – unable to discontinue caffeine consumption for at least 8 h before and during the testing •History or any other clinical condition, judged to be a contraindication for participation in the study as judged by the PI •Loss of 250 mL or more of blood within 3 months prior to screening •Any abnormalities on lab or urine results outside the normal range, deemed clinically significant by the investigator (and with written consent of the sponsor)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of nebulised RPL554 at 2 single inhaled doses of 0.036 mg/kg (12X) and 0.072 mg/kg (24X) in allergic asthmatics using standard safety measures with intensive monitoring of any potential cardiovascular effects.;Secondary Objective: 1) To investigate the onset, magnitude and duration of RPL554’s bronchodilator effects in terms of maximal increase from baseline (pre-bronchodilator) Forced Expiratory Volume in the first second (FEV1) and the duration of the bronchodilator response (in FEV1) over time. 2) To investigate RPL554’s pharmacokinetics including the relationship between pharmacokinetics and bronchodilation; and the relationship between pharmacokinetics and any adverse events observed over time. ;Primary end point(s): A)Respiratory safety (i.e., effects on the upper and lower airways): -upper airways (nose): local irritation, sneezing, prolonged rhinorrhea, nasal congestion; -throat: local irritation, redness, dryness, effect on the voice; -lower airways (lung): coughing, dyspnoea/wheeze, clinically relevant decreases in breathing frequency and/or peripheral oxygen saturation (measured by pulse-oximetry during nebulisation) and/or decreases in spirometry (FEV1). B) Gastrointestinal safety/tolerability (i.e., nausea, vomiting, and abdominal discomfort or pain and/or diarrhoea). C) Cardiovascular safety (i.e., clinically relevant effects on heart rate & rhythm, and conduction times; and sitting blood pressure (also see relevant section 6.1.1 on cardiovascular safety) -12-lead ECG and holter ECG (rhythm and conduction times- with particular care given to the QTc interval) at baseline, during dosing and at regular intervals up to approximately 12 h; -ECG telemetry during nebulisation up to approximately 2 h post-dosing; -Sitting blood pressure and heart rate at baseline and at regular intervals (approximately 5-10 min) during nebulisation up to 1 h post-dosing and subsequently at approximately 15 min intervals up to 4 h post | — |
Countries
Netherlands
Outcome results
None listed