Bioequivalence Study Between Levocetirizine Oral Disintegrating Tablet (ODT) and Levocetirizine Immediate Release Tablet (IRT)

NCT03555890 | Completed Phase 1 Results

• 1 other identifier: 204706
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rhinitis

Keywords

Oral disintegrating tablet; Levocetirizine; Immediate release tablet; Bioequivalence; Japanese subjects

Outcome Measures

Primary Outcomes (4)

• Part 1: Area Under the Concentration-time Curve (AUC) From Time Zero Time (Pre-dose) to the Time of Last Quantifiable Concentration (AUC[0-t]) of Levocetirizine

  Blood samples were collected to measure AUC(0-t) at indicated time-points. AUC(0-t) was calculated by the linear trapezoidal method (i.e., Linear Trapezoidal Linear Interpolation calculation method in Phoenix WinNonlin).

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose

• Part 2: AUC(0-t) of Levocetirizine

  Blood samples were collected to measure AUC(0-t) at indicated time-points. AUC(0-t) was calculated by the linear trapezoidal method (i.e., Linear Trapezoidal Linear Interpolation calculation method in Phoenix WinNonlin).

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose

• Part 1: Maximum Observed Concentration (Cmax) of Levocetirizine

  Blood samples were collected at indicated time points for analysis of Cmax. The values for Cmax were obtained directly from the concentration-time data.

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose

• Part 2: Cmax of Levocetirizine

  Blood samples were collected at indicated time points for analysis of Cmax. The values for Cmax were obtained directly from the concentration-time data.

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose

Secondary Outcomes (60)

• Part 1: Area Under the Concentration-time Curve From Zero Time (Pre-dose) Extrapolated to Infinite Time AUC(0-inf) of Levocetirizine

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36 and 48 hours post-dose

• Part 2: AUC(0-inf) of Levocetirizine

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36 and 48 hours post-dose

• Part 1: Time to First Occurrence of Cmax (Tmax) of Levocetirizine

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36 and 48 hours post-dose

• Part 2: Tmax of Levocetirizine

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36 and 48 hours post-dose

• Part 1: Apparent Terminal Phase Half-life (t1/2) of Levocetirizine

  Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36 and 48 hours post-dose

Study Arms (4)

Subjects of Group A: Part 1

EXPERIMENTAL

Subjects in Group A will be randomized to receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine ODT 5 mg with 150 mL water in fasted state in Period 2.

Drug: Levocetirizine IRT 5 mg; Drug: Levocetirizine ODT 5 mg

Subjects of Group B: Part 1

EXPERIMENTAL

Subjects in Group B will be randomized to receive levocetirizine ODT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 2.

Drug: Levocetirizine IRT 5 mg; Drug: Levocetirizine ODT 5 mg

Subjects of Group C: Part 2

EXPERIMENTAL

Subjects in Group C will be randomized to receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine ODT 5 mg without water in fasted state in Period 2.

Drug: Levocetirizine IRT 5 mg; Drug: Levocetirizine ODT 5 mg

Subjects of Group D: Part 2

EXPERIMENTAL

Subjects in Group D will be randomized to receive levocetirizine ODT 5 mg without water in fasted state in Period 1. After a washout period of at least 5 days, subjects will receive levocetirizine IRT 5 mg with 150 mL water in fasted state in Period 2.

Drug: Levocetirizine IRT 5 mg; Drug: Levocetirizine ODT 5 mg

Interventions

Levocetirizine IRT 5 mg DRUG

Levocetirizine IRT will be available as film-coated tablets. Subjects will receive a single dose of 5 mg levocetirizine IRT. Subjects will receive levocetirizine IRT with 150 mL water in both Part (1 and 2).

Subjects of Group A: Part 1; Subjects of Group B: Part 1; Subjects of Group C: Part 2; Subjects of Group D: Part 2

Levocetirizine ODT 5 mg DRUG

Levocetirizine ODT will be available as oral disintegrating tablet. Subjects will receive a single dose of 5 mg levocetirizine ODT. In Part 1, subjects will receive levocetirizine ODT with 150 mL water and in Part 2 subjects will receive levocetirizine ODT without water.

Subjects of Group A: Part 1; Subjects of Group B: Part 1; Subjects of Group C: Part 2; Subjects of Group D: Part 2

Eligibility Criteria

• Age: 20 Years - 55 Years
• Gender Eligibility Details: Healthy Japanese male subjects will be part of this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Zensei Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

GSK Investigational Site

Fukuoka, 812-0025, Japan

Location

MeSH Terms

Conditions

Rhinitis

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is 2-way crossover 2 part study. In Part 1, comparison of bioavailability of levocetirizine ODT and levocetirizine IRT taken with water in the fasted state will be done and In Part 2, comparison of bioavailability of levocetirizine ODT without water and levocetirizine IRT with water in the fasted state will be done.

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: June 14, 2018
• Study Start: May 18, 2018
• Primary Completion: September 17, 2018
• Study Completion: September 17, 2018
• Last Updated: June 2, 2020
• Results First Posted: September 12, 2019

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

JP (1)