bilastine updosing - characterization of underlying mechanisms

Conditions: Cold Contact Urticaria

Summary: this is a double-blind, triple cross-over, placebo-controlled study to assess the efficacy, mechanisms, and safety of treatment with the antihistamine bilastine in patients with cold contact urticaria (ccu). efficacy is primarily assessed by a change in critical stimulation time thresholds (cstt) and critical temperature thresholds (ctt) after treatment with different dosages of bilastine (20 mg, 40 mg, 80 mg). following a baseline period of 2-4 weeks, patients are randomized to either group a or group b. in group a they are given bilastine 20 mg, 40 mg, placebo and bilastine 80 mg for 7 days each followed by a 14-day washout period at a time. in group b they are given bilastine 80 mg, placebo, 40 mg and 20 mg for 7 days each followed by a 14-day washout period at a time. cstt and ctt testings are performed at each of 6 visits, skin microdialysis for the assessment of mast cell mediators is performed at v2, v3 and v6. visits for investigator's assessments are scheduled at day -14 to -28, day 0, day 7, day 28, day 49, and day 70. overall a max. of 20 subjects with cold contact urticaria will be enrolled.


Eligibility criteria:
inclusion criteria: * informed consent signed and dated * reliable method of contraception for both women of childbearing potential as well as man during the study and 3 months thereafter. a highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some iuds, sexual abstinence or vasectomised partner * outpatients with ccu for more than 6 weeks. urticaria symptoms must comprise wheal and itch. * age above 18 years. * no participation in other clinical trials 1 months before and after participation in this study exclusion criteria: * subjects who are inmates of psychiatric wards, prisons, or other state institutions. existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 amg (arzneimittelgesetz) * the presence of permanent severe diseases, especially those affecting the immune system, except urticaria and cold urticaria * the presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract) * history or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia * history or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy * ecg alterations of repolarisation (qtc prolongations \> 450ms) * blood pressure \>180/100 mmhg and/or heart rate \>100/min. * evidence of significant hepatic or renal disease (got and/or gpt 3 times above the upper reference value, serum creatinine 1.5 times above the upper reference value) * history of adverse reactions to bilastine or known hypersensitivity to bilastine or its ingredients * presence of active cancer which requires chemotherapy or radiation therapy * presence of alcohol abuse or drug addiction * intake of oral corticosteroids within 14 days prior to screening visit * use of depot corticosteroids or chronic systemic corticosteroids within 21 days prior to screening visit * use of systemic immunosupressants/immunomodulators like ciclosporine a, dapsone, methotrexate, mycophenolate, chloroquine, and comparable drugs within 28 days prior to screening visit * pregnancy or breast-feeding

Keywords: urticaria bilastine