Bilastine Updosing - Characterization of Underlying Mechanisms

Study Overview
=================
Brief 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.

Official Title
-----------------
Double-blind, Triple Cross-over, Placebo-controlled Study to Assess the Efficacy, Mechanisms, and Safety of Treatment With Bilastine 20 mg, 40 mg and 80 mg in Cold Contact Urticaria (CCU)

Conditions
-----------------
Cold Contact Urticaria

Intervention / Treatment
-----------------
* Drug: Bilastine
* Drug: Bilastine


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bilastine A<br>A: Crossover Bilastine 20 mg, Bilastine 40 mg, Placebo, Bilastine 80 mg | Drug: Bilastine<br>* Single dose, oral, 20 mg, 40 mg, 80 mg each for 7 days<br>|
| Active Comparator: Bilastine B<br>B: Crossover Bilastine 80 mg, Placebo, Bilastine 40 mg, Bilastine 20 mg | Drug: Bilastine<br>* Single dose, oral, 20 mg, 40 mg, 80 mg each for 7 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of a standard dose (20 mg) and higher than standard doses of bilastine (40 mg and 80 mg) on symptom development in CCU patients | 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). | 6 visits in 12-14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of a standard dose (20 mg) and higher than standard doses of bilastine (80 mg) on mast cell mediator release in CCU patients | Change in mast cell mediator release, including histamine and mast cell-derived cytokines (e.g. IL-1, IL-6, IL-8, IL-13, TNF) after standard dose treatment with bilastine (20 mg) compared to high dose bilastine (80 mg) and baseline. | Visit 2 (day 0), visit 3 (day 7) and visit 6 (day 70) | 
| Safety and tolerability following administration of bilastine to patients with cold contact urticaria | Safety and tolerability: This includes physical examination, routine safety laboratory assessments, clinical observation, vital signs and adverse event reporting | up to 14 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
urticaria, bilastine