Clinical trial NCT01081574: Pharmacokinetic Study of Bilastine in Children From 2 to < 12 Years of Age With Either Allergic Rhinoconjunctivitis (AR) or Chronic Urticaria (CU)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Allergic Rhinoconjunctivitis
Chronic Urticaria
Keywords: Allergic Rhinitis
Seasonal Allergic Rhinitis
Perennial Allergic Rhinitis
Urticaria
Chronic Idiopathic Urticaria
Allergy
Sneezing
Nasal Itching
Rhinorrhea
Nasal Congestion
Wheals
Hives
Skin itching
Flare
Erythema
Lead sponsor: Faes Farma, S.A.
Sponsor class: INDUSTRY
First posted: 2010-03-05
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 1 day (visit 3, Day 7)
Secondary outcomes:
measure: 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).
timeFrame: 5 weeks
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Subiaco
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin. Campus Virchow-Klinikum. Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunologie
city: Franfurt
country: Germany
facility: Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt
city: Kiel
country: Germany
facility: Universitäts-Hautklinik
city: Stockholm
country: Sweden
facility: Karolinska University Hospital. Astrid Lindgren's Hospital
city: Uppsala
country: Sweden
facility: Children's Hospital at Uppsala University Hospital
Study officials:
affiliation: International Coordinating Investigator. Charité - Universitätsmedizin Berlin (Germany)
name: Ulrich Wahn, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitäts-Hautklinik Kiel (Germany)
name: Regina Föster-Holst, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clínica Universitaria de Navarra (Spain)
name: Belén Sádaba, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska University Hospital
name: Gunilla Hedlin, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: J.W. Goethe-Universität Frankfurt (Germany)
name: Stefan Zielen, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital at Uppsala University Hospital (Sweden)
name: Lennart Nordvall, Prof. Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Hospital for Children (Australia)
name: Peter Le Souef, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Children's Hospital
name: Noel E Cranswick, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.
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.
citation: 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.