Randomised, Double-Blind, Placebo-Controlled Evaluation of the Safety and Duration of Action of 2 Single Inhaled Doses, 0.036 mg/kg (12X) and 0.072 mg/kg (24X), of RPL554, a Dual PDE 3/4 Inhibitor, in Allergic Asthmatics - Evaluation of Nebulized RPL554 in asthmatics

• Conditions: Allergic Asthma; MedDRA version: 12.1Level: LLTClassification code 10001705Term: Allergic asthma

• Registration Number: EUCTR2010-021349-36-NL
• Lead Sponsor: Verona Pharma plc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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 <10 pack-years)
•No history of anaphylaxis, or of severe food or medication allergy
•Haematology, clinical chemistry and urinalysis test results not deviating from the normal range to a clinically relevant extent as deemed by the investigator
•Negative results from urine drug and cotinine screens (for nicotine use)
•Negative screening for Hepatitis B, Hepatitis C and HIV
•Ability to communicate well with the investigator and to understand and comply with the requirements of the study
•Documented history of mild to moderate persistent asthma, first diagnosed by an MD at least 6 months prior to the screening visit and currently controlled by beta-agonists on an as needed” basis only
•Clinically stable asthma, i.e. stable asthma symptoms and baseline prebronchodilator FEV1 values within 10% (i.e. study day 1 compared to screening) (preferably measured at the same time of day ±3 h); stable use of as needed” Short-Acting Beta2 Agonist (SABA) but not on controller medication (see exclusion criteria)
•Pre-bronchodilator FEV1 =70% of predicted
•Documented bronchial hyperresponsiveness to inhaled Methacholine (MBr or MCh) with a PC20Meth of =8 mg/mL at screening
•Documented allergy by a standardized Skin Prick Test (SPT): i.e. a positive wheal response to one or more of the common airborne allergens: Grass or tree Pollen, House Dust Mite, D. Farinae, cat, dog, or horse-dander, Aspergillus Fumigatus, A. Alternata, Artemisia Vulgaris (in the past 1 year)
•Steroid-naïve, or not on inhaled/nasal corticosteroids for at least one month and 8 weeks of systemic therapy before the study
•No use of anti-IgE (omalizumab) in the past 6 months
•No systemic or aerosol use of the following: leukotriene receptor antagonists (LTRA), theophylline, long acting beta agonists (LABA), or antihistamine such as H1 receptor antagonist for 2 weeks before the study
•No nasal medications (steroids, antihistamines, cromones) for one month (for nasal steroids), or 2 weeks for other medications; xylomethazoline (1 week); nasal NaCl 0.9% allowed
•Signed informed consent
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified