Safety Study of Levocetirizine and Fexofenadine

Study Overview
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Brief Summary
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This Study is to comparison of Efficacy and Consistency of Action of Levocetirizine 5 mg once daily with Fexofenadine 60 mg twice daily in the histamine induced wheal, flare and itch Response.

Detailed Description
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This will be a randomized, double-blind, placebo-controlled study with intra-individual comparison of the histamine induced wheal and flare reaction. In September 2009, Fexofenadine was approved as an antihistamine against allergies in Japan and it is currently used widely. It has been approved in 120 countries, including the US, UK, France and Germany [11]. In Europe and the United States, fexofenadine is marketed at 120 mg once daily for allergic rhinitis and 180mg once daily for urticaria. In Japan, fexofenadine is marketed at 60 mg twice daily for both conditions. But is this dosage regimen as effective as levocetirizine, 5 mg once daily? The above described study from Takahashi et al, comparing 60 mg twice daily versus cetirizine 10 mg once daily suggests that it is not [4]. The aim of the study is to compare the efficacy and consistency of action of levocetirizine 5 mg once daily with fexofenadine 60 mg twice daily over a 24 hour period in the histamine induced wheal, flare and itch response. Furthermore, we would like to investigate whether a different between Japanese and Caucasian exists or not. Each volunteer will receive the study medication at time point 0 and 12 hour later. Skin Prick Test (SPT) will be performed in each volunteer using histamine (10 mg/ml), 15 minutes before drug admission (baseline) and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours afterwards. Volumetric optical scanning system and infrared camera will be used for objective evaluation of the wheal- and flare reduction. Additionally, measurement of the erythema diameter with a transparent ruler will be performed. The subjective intensity of itching will be assessed using a Visual Analogue Scale (VAS). To relate the pharmacokinetics of the drugs to their pharmacodynamics, blood samples for assay of drug concentrations will be taken at baseline and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours later. Subjects will undergo the same procedure on three separate occasions to receive each treatment option. The options are: placebo at time 0 hours + placebo at 12 hours, Levocetirizine 5mg at time 0 hours + placebo at 12 hours or fexofenadine 60mg at time 0 hours + fexofenadine 60mg at 12 hours. There will be a washout period of at least 6 days between the treatments.

Official Title
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Comparison of Efficacy and Consistency of Action of Levocetirizine 5 mg Once Daily With Fexofenadine 60 mg Twice Daily in the Histamine Induced Wheal, Flare and Itch Response

Conditions
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Pruritus, Chronic Urticaria, Allergic Rhinitis

Intervention / Treatment
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* Drug: Levocetirizine Oral Tablet
* Drug: Fexofenadine 60 Mg Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen (18) healthy male volunteers, including at least 6 persons of Japanese origin, will be recruited for this study Exclusion Criteria: None of the subjects will have taken oral antihistamines, antidepressants, antipsychotics or corticosteroids or applied topical antihistamines, corticosteroids or mast cell stabilizers to the skin for 2 weeks prior to testing. No subject shall perform physical exercise for 4 hours prior to the skin prick testing. Especially, Bronchial asthma, anaphylactic reactions in the history, use of beta-blockers, skin diseases in the test field are exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo per os at time 0 hours + placebo per os at 12 hours. | Drug: Placebo Oral Tablet<br> <br> * Other names: Lichtenstein;|
| Active Comparator: Levocetirizin<br>Levocetirizin 5mg at time 0 and placebo per os at 12 hours | Drug: Levocetirizine Oral Tablet<br> <br> Drug: Placebo Oral Tablet<br> <br> * Other names: Lichtenstein;|
| Active Comparator: Fexofenadine<br>Fexofenadine 60mg per os at time 0 hours + fexofenadine 60mg per os at 12 hours | Drug: Fexofenadine 60 Mg Oral Tablet<br> <br> * Other names: Telfast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pruritus as Assessed by the VAS Score | We measured drug concentrations and various aspects of skin provocation testing such as itch intensity and wheal size. Measurements made at each time point were as followed: Pruritus was assessed every 30 s for 10 min after SPT using a visual analogue scale (VAS) score with a 0 and 100 at the two ex- tremes of an unmarked 100 mm line with higher values indicating greater puritus. The mean VAS for each 10 min was calculated and used as a primary end Point. | up to 10 minutes after skin prick test performed 24 hours after drug administration | 
| Flaire Diameter (mm) | Flaire diameter was measured with a transparent ruler as the mean of the largest diameter and the diameter at right angles to this. | 24 hours per treatment | 
| Wheal Volume (cm3) | Wheal volume was measured by a non-contact three dimensional measurement system (PRIMOS contact, GFM Messtechnik GmbH, Teltow, Germany). | 24 hours per treatment |