A Combined Clinical Phase I/IIa Study of the Safety and Efficacy of Nebulised RPL554 in Healthy Subjects, Allergic Asthmatics, and Allergic Rhinitics - Phase I/IIa Evaluation of Nebulised RPL554

• Conditions: Allergic Asthma and Allergic Rhinitis; MedDRA version: 9.1Level: LLTClassification code 10001705Term: Allergic asthma; MedDRA version: 9.1Level: LLTClassification code 10001723Term: Allergic rhinitis

• Registration Number: EUCTR2008-005048-17-NL
• Lead Sponsor: Verona Pharma Plc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-11
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

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

Inclusion Criteria

1) General Inclusion Criteria for All Study Subjects (i.e., Healthy, Asthmatic, Rhinitic)
1.1) Males aged 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
1.2) Age between 18 and 55 years at screening
1.3) No clinically relevant history of cardiovascular (including arrhythmias) disease; no active hyperthyroidism
1.4) No clinically relevant history of chronic or malignant diseases (except for in situ basalioma)
1.5) Body mass index (BMI) between 18 and 33 kg/m2 (65-100 kg inclusive)
1.6) Systolic blood pressure (SBP) 90-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and heart rate (HR) 45-90 beats per minute (inclusive), after resting for 5 minutes in the supine position
1.7) No clinically significant findings on physical examination
1.8) 12-lead ECG without clinically relevant abnormalities
1.9) Non-smokers or ex-smokers (stopped for at least 6 months before screening, and <10 pack-years)
1.10) Hematology, clinical chemistry and urinalysis test results not deviating from the normal range to a clinically relevant extent as deemed by the investigator
1.11) Ability to communicate well with the investigator and to understand and comply with the requirements of the study
1.12) Signed informed consent
2) Specific for Healthy Subjects
2.1) No pulmonary or airway disease including asthma and clinically active rhinitis
2.2) Normal lung function: i.e. absence of airway obstruction, with FEV1 and FVC at least 90% of predicted and an FEV1/FVC ratio >80%
2.3) No concomitant medication use, except for vitamins at a usual dose, occasional use of paracetamol or (influenza) vaccinations; other medications at the discretion of the investigator and with the written consent of sponsor
3) Specific for Allergic Asthmatic Subjects
3.1) No clinically significant findings on physical examination other than allergy and mild to moderate persistent asthma
3.2) Documented history of mild to moderate persistent asthma, first diagnosed at least 6 months prior to the screening visit and currently controlled by beta-agonists on an as needed” basis only
3.3) Clinically stable asthma, i.e. stable use of as needed” Short-Acting Beta2 Agonist (SABA), stable asthma symptoms, and baseline FEV1 values within 15% of each other on all study days (measured at the same time of day +/- 3 hours)
3.4) Pre-bronchodilator FEV1 =70% of that predicted for the subject with a documented reversibility of at least 8% following 200-400 mcg inhaled salbutamol (i.e., an increase of 8% in pre-dose FEV1)
3.5) Documented bronchial hyper-responsiveness to inhaled Methacholine bromide (MCh) with a PC20MCh of =4 mg/mL
3.6) Documented allergy by a standardized Skin Prick Test (SPT): i.e. a positive wheal (a wheal response of at least 3 mm) 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
3.7) Steroid-naïve, or not on inhaled/nasal or systemic corticosteroids for at least one month of inhaled therapy and 8 weeks of systemic therapy before the study
3.8) No use of anti-IgE (omalizumab) in the past 6 months
3.9) 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
3.10) No nasal medications (stero

Exclusion Criteria

1) General Exclusion Criteria for All Study Subjects (i.e., Healthy, Asthmatic, Rhinitic)
1.1) 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
1.2) Treatment with another investigational drug within 3 months prior to screening
1.3) Known hypersensitivity to any excipients of the drug formulations
1.4) 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 than14 units/week for females)
1.5) 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
1.6) History of anaphylaxis or severe allergy for food or medication
1.7) Recent respiratory tract infections (within 3 weeks of screening and during study)
1.8) Loss of 500 mL or more of blood within 3 months prior to screening
1.9) Positive results for the HIV, HBV and HCV serology at screening
1.10) Positive results for urine drug and cotinine screens (for nicotine use)
1.11) Any abnormalities on lab or urine results outside the normal range, deemed clinically significant by the investigator (and with written consent of the sponsor)

2) Specific Exclusion Criteria for Healthy Subjects
2.1) Clinical evidence of asthma or any other pulmonary disease

3) Specific Exclusion Criteria for Allergic Asthmatic Subjects
3.1) Controller therapy with anti-IgE in the past 6 months, systemic corticosteroids in the past 8 weeks; intranasal corticosteroids in the past 1 month; leukotriene receptor antagonists, theophyllines or cromones in the past 2 weeks, antihistamines in the past 2 weeks, vasoconstrictors such as xylomethazoline (in the past week), and NaCl 0.9% allowed
3.2) Desensitization therapy in the past
3.3) Severe exacerbation requiring hospital evaluation and/or admission in the past 2 years
3.4) Unstable disease

4) Specific Exclusion Criteria for Allergic Rhinitic Subjects
4.1) Controller therapy with anti-IgE in the past 6 months, systemic corticosteroids in the past 8 weeks; intranasal corticosteroids in the past 1 month; leukotriene receptor antagonists or cromones in the past 2 weeks, antihistamines in the past 2 weeks, vasoconstrictors such as xylomethazoline (in the past week), and NaCl 0.9% allowed
4.2) Desensitization therapy in the past
4.3) Nasal surgery in the past
4.4) Evident or history of nasal polyps
4.5) Unstable disease, i.e., active allergic rhinitis (apart from stable, mild nasal congestion), needing controller therapy

Study & Design

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