Aim of the study is to evaluate RPL554*s safety in healthy, non-asthmatic subjects and consequently to assess RPL 554 safety and efficacy in allergic asthmatics and in allergic rhinitics.
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the safety of nebulized RPL554 in healthy subjects, allergic
asthmatics and allergic rhinitics using standard safety measures.
Secondary outcome
To investigate whether nebulized RPL554 possesses:
-Bronchodilator (increase in FEV1) and bronchoprotective activity (increase in
PC20 to inhaled methacholine), respectively, in patients with clinically stable
allergic asthma, not on controller medications and without regular use of
bronchodilators.
-Anti-inflammatory effects in subjects with allergic rhinitis not on controller
therapy following a standardized nasal challenge with a relevant allergen
(inhibition of the allergen-induced nasal eosinophilia in nasal brushes).
-To investigate RPL554*s effect on the following exploratory measures:
-Nasal composite symptom scores post-allergen (RPL554 versus placebo)
-To investigate RPL554*s pharmacokinetics in plasma and urine.
Background summary
RPL554, is an inhibitor of two subtypes (3 and 4) of phosphodiesterase (PDE)
enzymes. These two subtypes are known to be involved in modulating inflammatory
respiratory diseases, including allergic asthma and rhinitis. PDE 3 inhibitors
have bronchodilator effects, while PDE 4 inhibitors have anti-inflammatory
properties. Pharmacological evidence from animal experiments suggests that
RPL554 may have therapeutic potential in both allergic asthma and rhinitis.
Study objective
Aim of the study is to evaluate RPL554*s safety in healthy, non-asthmatic
subjects and consequently to assess RPL 554 safety and efficacy in allergic
asthmatics and in allergic rhinitics.
Study design
Stage 1: a randomized, placebo controlled, parallel and double blind study in
healthy volunteers.
Stage 2: an adaptive study with up to 4 potential dose levels in asthmatic
patients.
Stage 3A: a randomized, placebo-controlled, double blind cross over study with
two identical occasions in asthmatic patients.
Stage 3R: a randomized, placebo-controlled, double blind, crossover study with
two identical occasions in patients with allergic rhinits.
Intervention
RPL554 or placebo
Study burden and risks
During the screening clinical significant abnormalities might be discovered,
while during the study after the methacholine and nasal allergen challenge the
patients respectively get dyspnoea and local allergic reactions.
Suite 21 Alpha House, 100 Borough High Street
London SE1 1LB
United Kingdom
Suite 21 Alpha House, 100 Borough High Street
London SE1 1LB
United Kingdom
Listed location countries
Age
Inclusion criteria
Male volunteers: healthy, non-smokers
Female volunteers: healthy, post-menopausal, non-smokers
Asthmatic patients: history of allergic asthma for at least 6 months, stable allergic asthma, Pre-bronchodilator FEV1 >=70% of predicted, documented bronchial hyper-responsiveness to inhaled Methacholine bromide (MCh) with a PC20MCh of <=4 mg/mL, documented allergy by a standardized Skin Prick Test (SPT)
Patients with allergic rhinitis: Documented allergy by a standardized Skin Prick Test (SPT), History of allergic rhinitis for at least 6 months, clinically stable allergic rhinitis
Exclusion criteria
Volunteers: clinical significant abonormalities (females: potential fertile)
Asthmatic patients: unstable asthma, recent (<4 weeks) treatment with inhaled corticosteroids or with systemic corticosteriods (within 8 weeks), recent (within 4 weeks) or actual airways viral infection, clinical significant abonormalities (females potential fertile).
Rhinitic patients: unstable allergic rhinitis, history of nasal surgery, evidence of nasal polyps, clinical significant abonrmalities (females potential fertile)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-005048-17-NL |
| CCMO | NL25696.058.08 |