Oral Bioavailability of Bilastine

Study Overview
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Brief Summary
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The purpose of this study is to assess the absolute bioavailability of an oral bilastine formulation (test drug) compared to the endovenous administration of an IV bilastine formulation (control drug) in healthy volunteers.

Detailed Description
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Single centre, open label, cross-over, randomised, controlled, single dose study. The primary endpoint is the determination of plasma concentrations versus time (17 samples per subject at various time intervals after dosing) in order to assess the oral bioavailability of bilastine in healthy volunteers. Therefore the primary pharmacokinetic variable will be the area under the plasma concentration versus time curve from time zero to infinity (AUC 0-∞). Additionally the following pharmacokinetic variables will also be assessed: Cmax, AUC 0-t, tmax, Ae, Clr, t1/2. Additional objectives are to describe the safety and tolerability of a single administration of oral and endovenous bilastine in healthy volunteers. Twelve healthy volunteers will be included. Each volunteer will take in random order one single dose of 20 mg oral bilastine and 10 mg IV bilastine with a minimum washout period of 14 days between them. Bilastine plasma concentrations will be measured using a liquid chromatography/mass mass spectrometry (LC/MS/MS) micro method

Official Title
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Study to Assess Oral Bioavailability of Bilastine (Estudio de Biodisponibilidad Oral de Bilastina)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Bilastine
* Drug: Bilastine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers of either sex aged from ≥ 18 to ≤ 35 years of age. Body mass index between 19 and 29 Kg/m2. Non smokers. Judged to be in general good health based on medical history, physical examination and clinical laboratory tests. Able to communicate well with the investigator and to comply with the requirements of the entire study. Provision of written informed consent to participate. Exclusion Criteria: Pregnant or breast-feeding women or with a positive pregnancy test. Subjects who do not agree to use an adequate method of contraception during the study. Intake of another investigational medication in another clinical study within 4 months prior to the first study drug intake. Regular use of any prescribed medication including medicinal herbs or OTC medication within 4 weeks of dosing. A QTc> 430 ms in males and a QTc> 450 ms in females. A HR <55 bpm. Existence of any surgical or medical condition which, in the judgement of the investigator, might interfere with the absorption, distribution, metabolism or excretion of the IMP. Known allergy/hypersensitivity to the study drug or its inactive ingredients. 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). Presence of hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab) or HIV 1 or HIV 2 antibodies at screening. Subjects who have taken metabolic or transporter inducers/inhibitors during the 3 months prior to inclusion in the study. Donation or loss of greater than 200 mL of blood within 12 weeks before entry to the study. Blood transfusion within the prior 6 months to inclusion. Ingestion of citrus fruits and cranberries or any fruit juice within 7 days prior to first dose of study medication. Known current alcohol or drug abuse. Excessive consumption of xanthine containing foods or drinks. Mentally disabled subjects or subjects who by official order have been institutionalised must be excluded from participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bilastine 20 mg<br>Single dose 20 mg bilastine oral tablet. Test drug | Drug: Bilastine<br>* 20 mg oral tablet<br>|
| Active Comparator: Bilastine 10 mg<br>Single dose 10 mg Bilastine endovenous. Control drug | Drug: Bilastine<br>* 10 mg endovenous bilastine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the plasma concentration versus time curve from time zero to infinity (AUC 0-∞ ). | Bilastine bioavailability will be obtained from the oral AUC 0-∞ / endovenous AUC 0-∞ quotient. | 17 blood draws performed at: 0,25 - 0,5- 0,75 - 1 - 1,25 - 1,5 - 1,75 - 2 - 2,5 - 3 - 4 - 5 - 7 - 12 - 24 - 48 and 72 hours post administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Additional pharmacokinetic variables: Cmax, AUC 0-t, tmax, Ae, CLr and t ½ | Cmax: Maximum plasma concentration; the highest concentration observed during a dosage interval tmax: The time that Cmax was observed AUC 0-t: The area under the plasma concentration versus time curve from time zero to the last time point Ae: amount of accumulated unaltered drug in urine till the last time point Clr: Renal clearance t ½: Elimination halflife | 17 blood draws and urine collection during 72 hours post administration | 
| Safety and tolerability of a single dose administration of oral and endovenous bilastine | 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. | A last Follow up visit will be performed 7 days after last drug intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Oral bioavailability, absorption, AUC, Bioequivalence, Bioavailability study