Clinical trial NCT03555890: Bioequivalence Study Between Levocetirizine Oral Disintegrating Tablet (ODT) and Levocetirizine Immediate Release Tablet (IRT)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rhinitis
Keywords: Oral disintegrating tablet
Levocetirizine
Immediate release tablet
Bioequivalence
Japanese subjects
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Zensei Pharmaceutical Co., Ltd.
First posted: 2018-06-14
Enrollment: 72
Sex: MALE
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
measure: Part 2: AUC(0-t) of Levocetirizine
timeFrame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
measure: Part 1: Maximum Observed Concentration (Cmax) of Levocetirizine
timeFrame: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
measure: Part 2: Cmax of Levocetirizine
timeFrame: 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:
measure: Part 1: Area Under the Concentration-time Curve From Zero Time (Pre-dose) Extrapolated to Infinite Time AUC(0-inf) of Levocetirizine
timeFrame: 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
measure: Part 2: AUC(0-inf) of Levocetirizine
timeFrame: 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
measure: Part 1: Time to First Occurrence of Cmax (Tmax) of Levocetirizine
timeFrame: 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
measure: Part 2: Tmax of Levocetirizine
timeFrame: 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
measure: Part 1: Apparent Terminal Phase Half-life (t1/2) of Levocetirizine
timeFrame: 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
measure: Part 2: t1/2 of Levocetirizine
timeFrame: 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
measure: Part 1: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) of Levocetirizine
timeFrame: 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
measure: Part 2: %AUCex of Levocetirizine
timeFrame: 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
measure: Part 1: Apparent Clearance Following Oral Dosing (CL/F) of Levocetirizine
timeFrame: 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
measure: Part 2: CL/F of Levocetirizine
timeFrame: 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
measure: Part 1: Apparent Volume of Distribution Following Oral Dosing (Vz/F) of Levocetirizine
timeFrame: 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
measure: Part 2: Vz/F of Levocetirizine
timeFrame: 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
measure: Part 1: Elimination Rate Constant (Kel) (lambda_z) of Levocetirizine
timeFrame: 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
measure: Part 2: Kel (lambda_z) of Levocetirizine
timeFrame: 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
measure: Part 1: Mean Residence Time (MRT) of Levocetirizine
timeFrame: 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
measure: Part 2: MRT of Levocetirizine
timeFrame: 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
measure: Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 18 days
measure: Part 2: Number of Participants With AEs and SAEs
timeFrame: Up to 18 days
measure: Part 1: Change From Baseline in Albumin and Total Protein Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Albumin and Total Protein Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Amylase Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Amylase Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, High Density Lipids Cholesterol, Potassium, Low Density Lipids Cholesterol, Sodium, Phosphorus Inorganic, Triglycerides and Urea/Blood Urea Nitrogen (BUN) Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Calcium, Cholesterol, Chloride, Glucose, High Density Lipids Cholesterol, Potassium, Low Density Lipids Cholesterol, Sodium, Phosphorus Inorganic, Triglycerides and Urea/BUN Levels
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Platelet Count and White Blood Cell Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Platelet Count and White Blood Cell Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change Form Baseline in Hematocrit
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change Form Baseline in Hematocrit
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Mean Corpuscle Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Mean Corpuscle Hemoglobin
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Mean Corpuscle Volume
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Mean Corpuscle Volume
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Red Blood Cell Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Red Blood Cell Count
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Change From Baseline in Reticulocytes
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 2: Change From Baseline in Reticulocytes
timeFrame: Baseline (Day 1, Pre-dose) and 48 hours post-dose
measure: Part 1: Number of Participants With Urinalysis Results by Dipstick Method
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 2: Number of Participants With Urinalysis Results by Dipstick Method
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 1: Urine Potential of Hydrogen (pH)
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 2: Urine Potential of Hydrogen (pH)
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 1: Urine Specific Gravity
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 2: Urine Specific Gravity
timeFrame: Pre-dose (Day 1) and 48 hours post-dose
measure: Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 2: Change From Baseline in SBP and DBP
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 1: Change From Baseline in Heart Rate
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 2: Change From Baseline in Heart Rate
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 1: Change From Baseline in Body Temperature
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 2: Change From Baseline in Body Temperature
timeFrame: Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose
measure: Part 1: Change From Baseline in Heart Rate (12-Lead Electrocardiogram [ECG])
timeFrame: Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose
measure: Part 2: Change From Baseline in Heart Rate (ECG)
timeFrame: Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose
measure: Part 1: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval
timeFrame: Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose
measure: Part 2: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval
timeFrame: Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: