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.

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.

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.