Source: Annual Congress 2010 - New treatments for asthma and COPD
Disease area: Airway diseases

Abstract

Background: UR-63325 is a new H₄ receptor (H₄R) antagonist for treatment of asthma and allergic rhinitis. A first into man (FiM) study concluded good tolerability of single doses in healthy volunteers (HV), providing detailed pharmacokinetic (PK) and pharmacodynamic (PD) data. A multiple ascending dose (MAD) study is ongoing. Because of lack of clinical data on other H₄R antagonists, the best approach to a proof of concept (PoC) study on the activity of UR-63325 in allergic conditions has been sought, considering the new mechanism of action (MoA) and available PK/PD data.
Objectives: To design the best approach to assess the antiallergic effect of UR-63325 in a clinical setting, and to calculate the best dose to test using data from previous studies in HV.
Methods: A detailed analysis of the MoA identified the key processes where UR-63325 could better show antiallergic effect and key activity markers to measure in the PoC study. A PK/PD model with FiM data was used to choose UR-63325 dosing schedule to ensure relevant H₄R antagonism during the treatment period.
Results: Through PK/PD modelling, daily dosing of 40 mg of UR-63325 for 7 days was expected to reach sustained H₄R blockade above 75% for 24 hours and was proposed for the PoC study based on expected clinically relevant activity. Preliminary results from MAD study will be used to validate the model. A nasal challenge in volunteers with seasonal allergic rhinitis has been adapted to improve sensitivity of the main measurement.
Conclusions: The design of the PoC study of UR-63325 has been guided by MoA and PK/PD to increase chances of obtaining clinically relevant data on potential antiallergic activity.

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Citations should be made in the following way:
R. Vives, J. Peña, J. Alfon, C. Salcedo, J. Rios, C. Pontes, M. Merlos (Palau-solità i Plegamans, Barcelona, Spain). Biomarker-guided design to test clinical proof of concept in allergic respiratory diseases of UR-63325, a new H₄R antagonist. Eur Respir J 2010; 36: Suppl. 54, 1169

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