Bilastine Updosing - Characterization of Underlying Mechanisms (BUCUM)

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)

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.

Study Overview

• Status: Completed
• Conditions: Cold Contact Urticaria
• Intervention / Treatment: Drug: Bilastine

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite-Universitatsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bilastine A; A: Crossover Bilastine 20 mg, Bilastine 40 mg, Placebo, Bilastine 80 mg	Drug: Bilastine; Single dose, oral, 20 mg, 40 mg, 80 mg each for 7 days
Active Comparator: Bilastine B; B: Crossover Bilastine 80 mg, Placebo, Bilastine 40 mg, Bilastine 20 mg	Drug: Bilastine; Single dose, oral, 20 mg, 40 mg, 80 mg each for 7 days

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Faes Farma, S.A.
• Investigators: Principal Investigator: Marcus Maurer, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 30, 2010
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Estimate): May 31, 2012
• Last Update Submitted That Met QC Criteria: May 30, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: urticaria; bilastine
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria
• Other Study ID Numbers: BUCUM 2010; 2010-019344-39 (EudraCT Number)