Different Level of Single-dose and Multiple-dose Bilastine PK Study in Chinese Population

Study Overview
=================
Brief Summary
-----------------
This is a single-dose and multiple-dose, open-label, single-centre pharmacokinetic (PK) study which will be conducted in Phase I Clinical Trial Centre, Chinese University of Hong Kong, to evaluate pharmacokinetics (PK) of different levels of single-dose and multiple-dose of bilastine in healthy Chinese subjects.

Detailed Description
-----------------
This is a single-dose and multiple-dose, open-label, single-centre pharmacokinetic (PK) study, to evaluate pharmacokinetics (PK) of different levels of single-dose and multiple-dose of bilastine in healthy Chinese subjects. Total 24 subjects will be enrolled into the study and divided into 2 cohorts, 12 subjects in each cohort. Single-dose only cohort treatment duration is 1 day and receive a single dose of 40 mg of bilastine then collect PK blood sample. Single-dose followed by multiple-dose cohort treatment duration of this cohort is 9 days. Subjects will receive a single dose of bilastine 20 mg on the morning of Day 1; and six doses of bilastine 20 mg in the morning from Day 4 to Day 9 and collect PK blood samples. The primary objective of the study is to determine the PK properties of orally administered bilastine in healthy Chinese population. The secondary objective of the study is to evaluate the safety and tolerability of bilastine administered as a single and multiple doses in healthy Chinese subjects.

Official Title
-----------------
A Different Level of Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics of Bilastine in a Chinese Population

Conditions
-----------------
Pharmacokinetics

Intervention / Treatment
-----------------
* Drug: Bilastine 40mg single dose
* Drug: Bilastine 20mg single-dose followed by multiple-dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ethnic Chinese males and females between 18 and 45 years of age (inclusive). Having voluntarily given their informed consent to participate in the study after receiving information about the design, aims and potential risks that could result from the study and being informed that they could refuse to take part in or withdraw from the study at any time. Body mass of no less than 50 kg. Body mass index: 19 to 24 kg/m2 (inclusive). No clinically significant abnormal findings from the physical examination, vital signs check, electrocardiogram (ECG), medical history, or clinical laboratory results during screening and pre-dosing of Day 1. A negative screen for HIV and hepatitis B. A negative urine or breathalyzer screen for alcohol and negative urine screen for drugs of abuse. Are non-tobacco / nicotine users (within 3 months prior to screening visit). A negative serum pregnancy test for female subjects. Subjects who are willing to comply with the contraception restrictions for this study: True abstinence. Barrier methods with spermicidal use. The use of barrier contraceptives should always be supplemented with the use of a spermicide, where available. Intrauterine devices: intrauterine device with the use of condom or spermicide. Sterilization of male subjects (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). Exclusion Criteria: History of clinically significant gastrointestinal, renal, hepatic, neurologic, haematological, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, jeopardises the safety of the subject or will impact the validity of the study results. History of allergic or adverse response to antihistamine drugs. Participated in a clinical trial within 90 days prior to screening. Donated blood within 90 days prior to screening. Donated plasma within 90 days prior to screening. Abnormal diet or substantial changes in eating habits within 30 days prior to screening. Used any prescription medication within 14 days prior to or during screening, especially any known P-glycoprotein transporter inhibitors agents (ketoconazole, erythromycin, ciclosporin, digoxin, etc.). Used any prescription or any over-the-counter medication, herbal or traditional Chinese medication within 7 days prior to or during screening. Intake of grapefruit or any other citrus fruit, fruit juice or cranberries within 72 hours prior to study drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bilastine 40mg single dose<br>12 eligible subjects will be allocated to this arm and receive a single dose of 40 mg of bilastine | Drug: Bilastine 40mg single dose<br>* Single-dose only cohort treatment duration is 1 day. After the screening period, eligible subjects will be allocated to receive a single dose of 40 mg of bilastine<br>|
| Experimental: Bilastine 20mg multiple dose<br>12 eligible subjects will be allocated to this arm and receive a single dose of bilastine 20 mg on Day 1 and six doses of bilastine 20 mg from Day 4 to Day 9 | Drug: Bilastine 20mg single-dose followed by multiple-dose<br>* Single-dose followed by multiple-dose cohort treatment duration of this cohort is 9 days. Subjects will receive a single dose of bilastine 20 mg on the morning of Day 1; and six doses of bilastine 20 mg in the morning from Day 4 to Day 9.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (Cmax) | observed maximum plasma concentration | day1, day4 to day9 | 
| Pharmacokinetic (tmax) | time to reach Cmax | day1, day4 to day9 | 
| Pharmacokinetic (λz) | terminal rate constant | day1, day4 to day9 | 
| Pharmacokinetic (t½) | terminal half-life | day1, day4 to day9 | 
| Pharmacokinetic [AUC(0-24)] | area under the plasma concentration-time curve from zero to 24 hours after study drug administration | day1 | 
| Pharmacokinetic [AUC(0-last)] | from time zero to the time of last quantifiable concentration | day1 | 
| Pharmacokinetic [AUC(0-inf)] | from time zero extrapolated to infinity | day1 | 
| Pharmacokinetic (CL/F) | apparent systemic clearance following oral dosing | day1, day4 to day9 | 
| Pharmacokinetic (Vz/F) | apparent volume of distribution during terminal phase following oral dosing | day1, day4 to day9 | 
| Pharmacokinetic [AUC(0-inf)/D] | dose-normalized AUC(0-inf) | day1 | 
| Pharmacokinetic (Cmax/D) | dose-normalized Cmax | day1 | 
| Pharmacokinetic (Cavg) | average concentration over the study drug interval | day4 to day9 | 
| Pharmacokinetic [AUC(0-tau)] | area under the plasma concentration-time curve during the dosing interval following multiple dosing | day4 to day9 | 
| Pharmacokinetic (FI) | fluctuation index | day4 to day9 | 
| Pharmacokinetic (LI) | linearity index | day4 to day9 | 
| Pharmacokinetic [RAUC(0-tau)] | accumulation ratio for AUC(0-tau) | day4 to day9 | 
| Pharmacokinetic (RCmax) | accumulation for Cmax | day4 to day9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Safety will be evaluated with summary of Adverse Events | day1 to day16 |