Pharmacokinetic Study of Bilastine in Children From 2 to < 12 Years of Age With Either Allergic Rhinoconjunctivitis (AR) or Chronic Urticaria (CU)

A Multicentre, International, Adaptive, Open-label, Repeated Administration Pharmacokinetic Study of Bilastine in Children From 2 to <12 Years of Age With Allergic Rhinoconjunctivitis or Chronic Urticaria

The conduct of this clinical trial is aimed at determining the most suitable dose regimen for children in different age groups, and secondarily to assess the safety and tolerability of bilastine in this paediatric population subset.

Study Overview

• Status: Completed
• Conditions: Chronic Urticaria; Allergic Rhinoconjunctivitis
• Intervention / Treatment: Drug: Bilastine

Detailed Description

The objective of this study is to assess the pharmacokinetics of bilastine in children (aged 2 to <12 years) with allergic rhinoconjunctivitis (seasonal allergic rhinitis [SAR] and/or perennial allergic rhinitis [PAR]) or chronic urticaria (CU) in order to ascertain that the systemic exposure attained with a dose of 10 mg/QD or lower is comparable to that achieved in adults and adolescents administered with a dose of 20 mg/QD.

Additional objectives are to describe the safety and tolerability of a repeated administration of bilastine in children with AR or CU.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
  • Western Australia
    • Subiaco, Western Australia, Australia, 6840
      • Princess Margaret Hospital for Children
• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedizin. Campus Virchow-Klinikum. Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunologie
  • Franfurt, Germany, 60590
    • Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt
  • Kiel, Germany, 24105
    • Universitäts-Hautklinik
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital. Astrid Lindgren's Hospital
  • Uppsala, Sweden, 751 85
    • Children's Hospital at Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 9 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Either sex aged from ≥ 2 to < 12 years of age. Female subjects must not be of child bearing potential.
2. Height and weight within a majority range (e.g., 25th through 75th percentile) of the subject's age and sex as provided in national tables.
3. Documented history of SAR/PAR or CU at the time of inclusion. Subjects must be symptomatic at screening as judged by the investigator.
4. A documented positive skin prick test or IgE test (RAST) for at least one seasonal or perennial allergen in children with AR obtained within the 12 months prior to inclusion.
5. Excepting AR or CU, judged to be in general good health based on medical history, physical examination and clinical laboratory tests, with a QTc duration on the ECG recorded at screening within the normal range (≤ 440 msec).
6. Written informed consent signed by the legal representative of the minor (his/her parent(s) or a person legally appointed if different from parent(s)) and, where applicable, assent signed by the child, according to local regulations.

Exclusion Criteria:

1. Female subjects of childbearing potential. If menarche occurs after study enrolment and during the dosing period, the subject should be discontinued from the treatment and followed up for safety as per protocol. Occurrence of menarche in the course of the study should always be documented.
2. Intake of another investigational medication in another clinical study within 30 days prior to the first study drug intake.
3. Clinically significant ECG abnormalities as judged by the investigator (e.g., Wolff-Parkinson-White [WPW] syndrome, long QT syndrome).
4. Known allergy/hypersensitivity to the study drug or its inactive ingredients.
5. Any clinical conditions or circumstances that in the opinion of the investigator would make the subject unsuitable for the study (e.g., hepatic impairment, renal impairment, mental impairment, cardiac disease).
6. Subjects with known positive Hepatitis B surface antigen (Hbs Ag), or Hepatitis C antibody or who are known to be human immunodeficiency virus (HIV) positive. No testing will be required for this study.

7. Subjects who are expected to take during the study period or have taken any of the following medications prior to inclusion in the study and have not complied with the specified wash out period of 7 days unless otherwise noted:

   • Oral corticosteroids.
   • Oral antihistamines: loratadine, desloratadine, and fexofenadine.
   • Anti-leukotrienes
   • Amoxicillin, benzylpenicillin, and macrolide antibiotics and imidazolic antifungals (systemic)
   • Omeprazol
   • Aspirin, ibuprofen
   • Carbamazepine
   • St. John's Wort (15 days)
8. Hypersensitivity to H1 antihistamines or benzimidazoles.
9. Ingestion of citrus fruits and cranberries or any fruit juice or any other well known PgP or organic anion transporter polypeptide (OATP) inhibitor, inducer, or substrate (see Appendix C) within 7 days prior to first dose of study medication.
10. Mentally disabled minors or Minors who by official order have been institutionalised (e.g., in orphanages) must be excluded from participation.
11. Minors who explicitly refuse to take part in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg Bilastine once daily for 7 days; 10 mg Bilastine dispersible oral tablet	Drug: Bilastine; 10 mg/qd/ 7 days.Oral dispersible tablets; Other Names: Bilaxten

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective is to assess the pharmacokinetics of bilastine in children (aged 2 to <12 years) with allergic rhinoconjunctivitis (seasonal allergic rhinitis and/or perennial allergic rhinitis [SAR/PAR]) or chronic urticaria (CU)	Determination of plasma concentrations versus time (between 1 and 6 samples per subject at various time intervals after dosing according to an optimised sampling protocol) in order to perform a population pharmacokinetic analysis. For Group A, samples of venous blood will be just prior to dose administration, and at 0.25, 0.5, 0.8, 1.0, 1.2, 1.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, and 24.0 hours after dose administration. For Group B samples of venous blood will be just prior to dose administration, and at 0.25, 0.5, 1.0, 1.5, 3.0, 6.0, 8.0, 10.0, and 12.0 hours after dose administration.	1 day (visit 3, Day 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary objectives are to describe the safety and tolerability of a repeated administration of bilastine in the aforementioned paediatric subset with allergic rhinoconjunctivitis (SAR/PAR) or chronic urticaria (CU).	Safety will be assessed during the study by monitoring adverse events (AEs), clinical laboratory test results (urinalysis, blood chemistry, and haematology), vital signs (including blood pressure, respiration, temperature, and heart rate, supine and standing), electrocardiogram (ECG) results, and abnormal findings upon physical examination.	5 weeks

Collaborators and Investigators

• Sponsor: Faes Farma, S.A.
• Investigators: Principal Investigator: Ulrich Wahn, Prof. Dr., International Coordinating Investigator. Charité - Universitätsmedizin Berlin (Germany); Principal Investigator: Regina Föster-Holst, Prof. Dr., Universitäts-Hautklinik Kiel (Germany); Principal Investigator: Belén Sádaba, Dr., Clínica Universitaria de Navarra (Spain); Principal Investigator: Gunilla Hedlin, Prof. Dr., Karolinska University Hospital; Principal Investigator: Stefan Zielen, Prof. Dr., J.W. Goethe-Universität Frankfurt (Germany); Principal Investigator: Lennart Nordvall, Prof. Dr, Children's Hospital at Uppsala University Hospital (Sweden); Principal Investigator: Peter Le Souef, Prof. Dr., Princess Margaret Hospital for Children (Australia); Principal Investigator: Noel E Cranswick, Prof. Dr., Royal Children's Hospital, Melbourne, Australia

Publications and helpful links

General Publications

• Bachert C, Kuna P, Sanquer F, Ivan P, Dimitrov V, Gorina MM, van de Heyning P, Loureiro A; Bilastine International Working Group. Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patients. Allergy. 2009 Jan;64(1):158-65. doi: 10.1111/j.1398-9995.2008.01813.x.
• Jauregizar N, de la Fuente L, Lucero ML, Sologuren A, Leal N, Rodriguez M. Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine. Clin Pharmacokinet. 2009;48(8):543-54. doi: 10.2165/11317180-000000000-00000.
• Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, Antepara I, Jauregui I, Valiente R; Bilastine International Working Group. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy. 2010 Apr;65(4):516-28. doi: 10.1111/j.1398-9995.2009.02217.x. Epub 2009 Oct 23.
• Horak F, Zieglmayer P, Zieglmayer R, Lemell P. The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber. Inflamm Res. 2010 May;59(5):391-8. doi: 10.1007/s00011-009-0117-4. Epub 2009 Nov 27.
• Kuna P, Bachert C, Nowacki Z, van Cauwenberge P, Agache I, Fouquert L, Roger A, Sologuren A, Valiente R; Bilastine International Working Group. Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double-blind, parallel-group study. Clin Exp Allergy. 2009 Sep;39(9):1338-47. doi: 10.1111/j.1365-2222.2009.03257.x. Epub 2009 May 4.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: March 4, 2010
• First Submitted That Met QC Criteria: March 4, 2010
• First Posted (Estimate): March 5, 2010

Study Record Updates

• Last Update Posted (Estimate): September 26, 2012
• Last Update Submitted That Met QC Criteria: September 25, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Allergy; Allergic Rhinitis; Sneezing; Urticaria; Hives; Chronic Idiopathic Urticaria; Rhinorrhea; Wheals; Flare; Erythema; Seasonal Allergic Rhinitis; Perennial Allergic Rhinitis; Nasal Itching; Nasal Congestion; Skin itching
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Skin Diseases, Vascular; Hypersensitivity; Conjunctival Diseases; Conjunctivitis; Conjunctivitis, Allergic; Urticaria; Chronic Urticaria
• Other Study ID Numbers: BILA 3009/PED; 2009-012013-22 (EudraCT Number)