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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Part 1: Maximum Observed Concentration (Cmax) of Levocetirizine
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Subjects of Group A: Part 1
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.
干预措施: Levocetirizine IRT 5 mg (Drug)
Subjects of Group A: Part 1
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.
干预措施: Levocetirizine ODT 5 mg (Drug)
Subjects of Group B: Part 1
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.
干预措施: Levocetirizine IRT 5 mg (Drug)
Subjects of Group B: Part 1
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.
干预措施: Levocetirizine ODT 5 mg (Drug)
Subjects of Group C: Part 2
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.
干预措施: Levocetirizine IRT 5 mg (Drug)
Subjects of Group C: Part 2
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.
干预措施: Levocetirizine ODT 5 mg (Drug)
Subjects of Group D: Part 2
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.
干预措施: Levocetirizine IRT 5 mg (Drug)
Subjects of Group D: Part 2
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.
干预措施: Levocetirizine ODT 5 mg (Drug)
结局指标
主要结局
Part 1: Maximum Observed Concentration (Cmax) of Levocetirizine
时间窗: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
Blood samples were collected at indicated time points for analysis of Cmax. The values for Cmax were obtained directly from the concentration-time data.
Part 2: Cmax of Levocetirizine
时间窗: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
Blood samples were collected at indicated time points for analysis of Cmax. The values for Cmax were obtained directly from the concentration-time data.
Part 2: AUC(0-t) of Levocetirizine
时间窗: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
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).
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
时间窗: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose
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).
次要结局
- Part 1: Mean Residence Time (MRT) 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: 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 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)
- Part 2: %AUCex 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: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) 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: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Amylase Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Platelet Count and White Blood Cell Count(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Kel (lambda_z) 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: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 18 days)
- 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(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Platelet Count and White Blood Cell Count(Baseline (Day 1, Pre-dose) 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 2: 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)
- Part 1: Apparent Clearance Following Oral Dosing (CL/F) 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 Volume of Distribution Following Oral Dosing (Vz/F) 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: Vz/F 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: Number of Participants With AEs and SAEs(Up to 18 days)
- Part 2: Change From Baseline in Albumin and Total Protein Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change Form Baseline in Hematocrit(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change Form Baseline in Hematocrit(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: CL/F 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: Elimination Rate Constant (Kel) (lambda_z) 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: Change From Baseline in Albumin and Total Protein Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Amylase Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- 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(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Mean Corpuscle Hemoglobin(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Mean Corpuscle Hemoglobin(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Reticulocytes(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: MRT 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: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Number of Participants With Urinalysis Results by Dipstick Method(Pre-dose (Day 1) and 48 hours post-dose)
- Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 1: Change From Baseline in Heart Rate(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 2: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval(Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose)
- Part 2: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Change From Baseline in Red Blood Cell Count(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Urine Potential of Hydrogen (pH)(Pre-dose (Day 1) and 48 hours post-dose)
- Part 2: Urine Potential of Hydrogen (pH)(Pre-dose (Day 1) and 48 hours post-dose)
- Part 2: Change From Baseline in SBP and DBP(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 1: Change From Baseline in Mean Corpuscle Volume(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Red Blood Cell Count(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Change From Baseline in Reticulocytes(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 2: Urine Specific Gravity(Pre-dose (Day 1) and 48 hours post-dose)
- Part 2: Change From Baseline in Heart Rate(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 2: Change From Baseline in Body Temperature(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 1: Change From Baseline in Heart Rate (12-Lead Electrocardiogram [ECG])(Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose)
- Part 2: Change From Baseline in Mean Corpuscle Volume(Baseline (Day 1, Pre-dose) and 48 hours post-dose)
- Part 1: Number of Participants With Urinalysis Results by Dipstick Method(Pre-dose (Day 1) and 48 hours post-dose)
- Part 1: Urine Specific Gravity(Pre-dose (Day 1) and 48 hours post-dose)
- Part 1: Change From Baseline in Body Temperature(Baseline (Day 1, Pre-dose) and 1, 24, 48 hours post-dose)
- Part 2: Change From Baseline in Heart Rate (ECG)(Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose)
- Part 1: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval(Baseline (Day 1, Pre-dose) and 1, 48 hours post-dose)