Last updated: 07/17/2024 17:19:06

Bioequivalence study between levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate release tablet (IRT)

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GSK study ID

204706

See study documents

Clinicaltrials.gov ID

NCT03555890

See results summary

EudraCT ID

Not applicable

EU CT Number

Not applicable

Trial status

Completed

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official title: A single centre, single dose, open-label, randomized, 2-part, 2-way crossover study to determine the bioequivalence of levocetirizine oral disintegrating tablet given with water and without water compared to levocetirizine immediate release tablet in healthy Japanese male subjects

Trial description: This study will be an open-label, randomized 2-way cross-over study to evaluate bioequivalence study between levocetirizine ODT and levocetirizine IRT in healthy Japanese male subjects. Approximately 48 subjects will participate in this study to receive a single dose treatments of levocetirizine ODT 5 milligram (mg) or levocetirizine IRT 5 mg. In Part 1, subjects will randomized in 1:1 ratio (12 in each Period) in Period 1 and 2 to receive single dose of levocetirizine ODT 5 mg with water or single dose levocetirizine IRT 5 mg with water in fasted state. In this part, comparison of bioavailability of levocetirizine ODT and levocetirizine IRT when taken with water in the fasted state will be assessed. In Part 2, subjects will be randomized in 1:1 ratio (12 in each Period) in Period 1 and 2 to receive single dose levocetirizine ODT 5 mg without water or single dose levocetirizine IRT 5 mg with water in fasted state. In this part, comparison of bioavailability of levocetirizine ODT without water and levocetirizine IRT with water in the fasted state will be assessed. There will be at least a 5-day wash out period between the intervention periods. The duration of each subject’s participation in each part will be approximately 7 weeks from screening to follow-up.

Primary purpose:

Treatment

Trial design:

Crossover Assignment

Masking:

None (Open Label)

Allocation:

Randomized

Primary outcomes:

Area under plasma concentration-time curve (AUC) from zero hours to last time of quantifiable concentration (AUC [0–t]) of levocetirizine: Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2,3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

AUC (0–t) of levocetirizine: Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2,3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Maximum plasma concentration (Cmax) of levocetirizine: Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Cmax of levocetirizine: Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Secondary outcomes:

Number of subjects with adverse events (AE) and serious AE (SAE) in Part 1

Timeframe: Up to Day 18

Number of subjects with AE and SAE in Part 2

Timeframe: Up to Day 18

Number of subjects with abnormal hematology parameters: Part 1

Timeframe: Up to Day 18

Number of subjects with abnormal hematology parameters: Part 2

Timeframe: Up to Day 18

Number of subjects with abnormal clinical chemistry parameters: Part 1

Timeframe: Up to Day 18

Number of subjects with abnormal clinical chemistry parameters: Part 2

Timeframe: Up to Day 18

Number of subjects with abnormal urinalysis parameters: Part 1

Timeframe: Up to Day 18

Number of subjects with abnormal urinalysis parameters: Part 2

Timeframe: Up to Day 18

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP): Part 1

Timeframe: Up to Day 18

Change from Baseline in SBP and DBP: Part 2

Timeframe: Up to Day 18

Change from Baseline in pulse rate: Part 1

Timeframe: Up to Day 18

Change from Baseline in pulse rate: Part 2

Timeframe: Up to Day 18

Change from Baseline in body temperature: Part 1

Timeframe: Up to Day 18

Change from Baseline in body temperature: Part 2

Timeframe: Up to Day 18

Change from Baseline in 12-lead Electrocardiogram (ECG): Part 1

Timeframe: Up to Day 18

Change from Baseline in 12-lead ECG: Part 2

Timeframe: Up to Day 18

AUC from time zero to infinity (AUC [0-inf]) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

AUC (0-inf) of levocetirizine: Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Time to Cmax (Tmax) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Tmax of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Terminal elimination half-life (t 1/2) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

T 1/2 of levocetirizine: Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Percentage of AUC (0-inf) obtained by extrapolation (percentage AUCex) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Percentage AUCex) of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Apparent clearance following oral dosing (CL/F) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

CL/F of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Apparent volume of distribution after oral administration (Vz/F) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Vz/F of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Elimination rate constant (kel) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Kel of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Mean residence time (MRT) of levocetirizine : Part 1

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

MRT of levocetirizine : Part 2

Timeframe: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose.

Interventions:

Drug: Levocetirizine IRT 5 mg

Drug: Levocetirizine ODT 5 mg

Enrollment:

Observational study model:

Not applicable

Primary completion date:

2018-17-09

Time perspective:

Not applicable

Clinical publications:

Hiroko Ino, Masanari Shiramoto, Takashi Etoh, Miwa Haranaka, Shin Irie, Takumi Terao, Hirofumi Ogura, Akira Wakamatsu, Keiko Hoyano, Atsushi Nakano.Levocetirizine oral disintegrating tablet: A randomized open-label crossover bioequivalence study in healthy Japanese volunteers.Clin Pharmacol Drug Devel.2020; DOI: 10.1002/cpdd.791 PMID: 32196954

Medical condition

Rhinitis

Product

levocetirizine

Collaborators

Zensei Pharmaceutical Co., Ltd.

Study date(s)

May 2018 to September 2018

Type

Interventional

Phase

Participation criteria

Sex

Male

Age

20 - 55 years

Accepts healthy volunteers

Yes

Subjects must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

Subjects with history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
Subjects with abnormal blood pressure as determined by the investigator.

Inclusion and exclusion criteria

Inclusion criteria:

Subjects must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
Subjects with body weight of >= 50 kilogram (kg) and body mass index (BMI) within the range of >=18.5 and <25.0 kg per meter square (m^2).
In male subjects contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Male subjects are eligible to participate if they agree to the following during the intervention period and until the completion of follow-ups: Refrain from donating sperm; Be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percentage per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant; Agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
Subjects must be non-smokers.
Subjects capable of giving signed informed consent.

Exclusion criteria:

Subjects with history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
Subjects with abnormal blood pressure as determined by the investigator.
Subjects with history of allergic rhinitis.
Subjects with ALT >1.5x upper limit of normal (ULN).
Subjects with bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percentage).
Subjects with current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Subjects with QTc >450 millisecond (msec).
Subjects with past or intended use of over-the-counter or prescription medication including vitamins, diet supplements (including St. John's wort), herbal medications within 14 days prior to first dosing or 5 half-lives (whichever is longer).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Current enrolment or past participation within 4 months prior to the first dosing day in this or any other clinical study involving an investigational study intervention or any other type of medical research (except for the subjects with no study intervention administered during any of those enrolment or participation).
The subject with positive serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum [TP] antibody tests), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
Subject with positive pre-study drug screen.
Subject with regular moderate alcohol consumption within 6 months prior to the study participation defined as: An average weekly intake of >14 units for males. One unit is equivalent to 360 milliliter (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled of spirits.
Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study.
History of donation of blood or blood products >= 400 mL within 3 months or >=200 mL within 1 month prior to the first dosing day.

Trial location(s)

Location

Status

Location

GSK Investigational Site

Fukuoka, Japan, 812-0025

Status

Study Complete

Study documents

Protocol

Available language(s): English

Download document(s)

Statistical analysis plan

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Completed

Actual primary completion date

2018-17-09

Actual study completion date

2018-17-09

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information

Not applicable

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