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

Allergic Rhinoconjunctivitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01081574
• Other study ID #: BILA 3009/PED
• Secondary ID: 2009-012013-22
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 4, 2010
• Last updated: September 25, 2012
• Start date: January 2010
• Est. completion date: June 2012

Study information

• Verified date: September 2012
• Source: Faes Farma, S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesSweden: Medical Products AgencySpain: Spanish Agency of MedicinesAustralia: National Health and Medical Research Council
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 11 Years

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Rhinoconjunctivitis
• Chronic Urticaria
• Conjunctivitis
• Conjunctivitis, Allergic
• Urticaria

Intervention

Drug:
• Bilastine
10 mg/qd/ 7 days.Oral dispersible tablets

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Subiaco	Western Australia
Germany	Charité - Universitätsmedizin. Campus Virchow-Klinikum. Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunologie	Berlin
Germany	Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt	Franfurt
Germany	Universitäts-Hautklinik	Kiel
Sweden	Karolinska University Hospital. Astrid Lindgren's Hospital	Stockholm
Sweden	Children's Hospital at Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Faes Farma, S.A.

Countries where clinical trial is conducted

Australia,  Germany,  Sweden, 

References & Publications (5)

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. — View Citation

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. — View Citation

Jauregizar N, de la Fuente L, Lucero ML, Sologuren A, Leal N, Rodríguez M. Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine. Clin Pharmacokinet. 2009;48(8):543-54. doi: 10.2165/11317180-000000000-00000. — View Citation

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. — View Citation

Zuberbier T, Oanta A, Bogacka E, Medina I, Wesel F, Uhl P, Antépara I, Jáuregui 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	Yes