Phase 1
Completed N=24
Bioequivalence Study Between Levocetirizine Oral Disintegrating Tablet (ODT) and Levocetirizine Immediate Release Tablet (IRT)
Source: ClinicalTrials.gov NCT03555890 ↗Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Sep 2019
Primary outcomePrimary: 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 — 1758.5; 1803.2 Hours*nanogram per milliliter (Hr*ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
1758.5; 1803.2 | — |
| PRIMARY Part 2: AUC(0-t) of Levocetirizine |
1809.9; 1843.5 | — |
| PRIMARY Part 1: Maximum Observed Concentration (Cmax) of Levocetirizine |
219.9; 235.4 | — |
| PRIMARY Part 2: Cmax of Levocetirizine |
191.5; 223.6 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve From Zero Time (Pre-dose) Extrapolated to Infinite Time AUC(0-inf) of Levocetirizine |
1812.9; 1852.5 | — |
| SECONDARY Part 2: AUC(0-inf) of Levocetirizine |
1869.5; 1900.2 | — |
| SECONDARY Part 1: Time to First Occurrence of Cmax (Tmax) of Levocetirizine |
0.5000; 0.7500 | — |
| SECONDARY Part 2: Tmax of Levocetirizine |
1.0000; 1.0000 | — |
| SECONDARY Part 1: Apparent Terminal Phase Half-life (t1/2) of Levocetirizine |
8.784; 8.544 | — |
| SECONDARY Part 2: t1/2 of Levocetirizine |
9.024; 8.933 | — |
| SECONDARY Part 1: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex) of Levocetirizine |
2.772; 2.500 | — |
| SECONDARY Part 2: %AUCex of Levocetirizine |
2.973; 2.779 | — |
| SECONDARY Part 1: Apparent Clearance Following Oral Dosing (CL/F) of Levocetirizine |
2.758; 2.699 | — |
| SECONDARY Part 2: CL/F of Levocetirizine |
2.675; 2.631 | — |
| SECONDARY Part 1: Apparent Volume of Distribution Following Oral Dosing (Vz/F) of Levocetirizine |
34.95; 33.27 | — |
| SECONDARY Part 2: Vz/F of Levocetirizine |
34.82; 33.91 | — |
| SECONDARY Part 1: Elimination Rate Constant (Kel) (lambda_z) of Levocetirizine |
0.07891; 0.08113 | — |
| SECONDARY Part 2: Kel (lambda_z) of Levocetirizine |
0.07681; 0.07760 | — |
| SECONDARY Part 1: Mean Residence Time (MRT) of Levocetirizine |
11.545; 11.417 | — |
| SECONDARY Part 2: MRT of Levocetirizine |
12.573; 12.272 | — |
| SECONDARY Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
0; 0; 0; 0 | — |
| SECONDARY Part 2: Number of Participants With AEs and SAEs |
6; 0; 0; 0 | — |
| SECONDARY Part 1: Change From Baseline in Albumin and Total Protein Levels |
1.6; 1.5; 2.7; 2.3 | — |
| SECONDARY Part 2: Change From Baseline in Albumin and Total Protein Levels |
1.2; 1.4; 1.8; 1.9 | — |
| SECONDARY Part 1: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels |
-0.8; -1.6; 0.5; 1.0; -0.1; -0.3 | — |
| SECONDARY Part 2: Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Levels |
-1.1; -2.3; -0.5; -0.7; 0.1; -0.1 | — |
| SECONDARY Part 1: Change From Baseline in Amylase Levels |
6.3; 7.2 | — |
| SECONDARY Part 2: Change From Baseline in Amylase Levels |
7.4; 7.1 | — |
| SECONDARY Part 1: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels |
0.214; 0.356; 0.143; -1.710; -1.9522; -1.9890 | — |
| SECONDARY Part 2: Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Levels |
-0.071; 0.036; -0.748; -0.619; -3.5913; -3.8746 | — |
| SECONDARY 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 |
0.032227; 0.018713; 0.117448; 0.054953; -0.9; -1.0 | — |
| SECONDARY 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 |
0.015594; 0.015926; 0.083506; 0.064925; -0.6; -0.5 | — |
| SECONDARY Part 1: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count |
-0.01; 0.01; -0.53; -0.52; -5.94; -5.96 | — |
| SECONDARY Part 2: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes and Total Neutrophils Count |
0.08; 0.04; -0.92; -0.74; -8.45; -8.07 | — |
| SECONDARY Part 1: Change From Baseline in Platelet Count and White Blood Cell Count |
-6.4; -11.4; -0.94; -1.26 | — |
| SECONDARY Part 2: Change From Baseline in Platelet Count and White Blood Cell Count |
-2.5; -2.9; -1.14; -1.06 | — |
| SECONDARY Part 1: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration |
2.2; 2.3; 2.3; 1.8 | — |
| SECONDARY Part 2: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration |
0.9; 0.9; 0.2; 0.5 | — |
| SECONDARY Part 1: Change Form Baseline in Hematocrit |
0.0036; 0.0043 | — |
| SECONDARY Part 2: Change Form Baseline in Hematocrit |
0.0023; 0.0019 | — |
| SECONDARY Part 1: Change From Baseline in Mean Corpuscle Hemoglobin |
-0.04; -0.03 | — |
| SECONDARY Part 2: Change From Baseline in Mean Corpuscle Hemoglobin |
-0.07; -0.07 | — |
| SECONDARY Part 1: Change From Baseline in Mean Corpuscle Volume |
-0.6; -0.5 | — |
| SECONDARY Part 2: Change From Baseline in Mean Corpuscle Volume |
-0.2; -0.3 | — |
| SECONDARY Part 1: Change From Baseline in Red Blood Cell Count |
0.078; 0.080 | — |
| SECONDARY Part 2: Change From Baseline in Red Blood Cell Count |
0.040; 0.041 | — |
| SECONDARY Part 1: Change From Baseline in Reticulocytes |
-0.0001; 0.0004 | — |
| SECONDARY Part 2: Change From Baseline in Reticulocytes |
-0.0001; -0.0004 | — |
| SECONDARY Part 1: Number of Participants With Urinalysis Results by Dipstick Method |
24; 24; 24; 24; 23; 24 | — |
| SECONDARY Part 2: Number of Participants With Urinalysis Results by Dipstick Method |
48; 47; 48; 47; 48; 47 | — |
| SECONDARY Part 1: Urine Potential of Hydrogen (pH) |
6.04; 6.06; 6.10; 6.02 | — |
| SECONDARY Part 2: Urine Potential of Hydrogen (pH) |
6.20; 6.11; 6.09; 6.00 | — |
| SECONDARY Part 1: Urine Specific Gravity |
1.0158; 1.0144; 1.0178; 1.0163 | — |
| SECONDARY Part 2: Urine Specific Gravity |
1.0156; 1.0179; 1.0160; 1.0159 | — |
| SECONDARY Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-2.0; 0.4; 0.0; 0.6; -1.2; 1.3 | — |
| SECONDARY Part 2: Change From Baseline in SBP and DBP |
0.2; -0.9; -1.9; -1.2; 0.7; 0.3 | — |
| SECONDARY Part 1: Change From Baseline in Heart Rate |
-2.3; -0.9; -0.8; -0.1; 0.8; 2.5 | — |
| SECONDARY Part 2: Change From Baseline in Heart Rate |
-1.5; -0.6; -1.9; 0.6; 1.5; 3.0 | — |
| SECONDARY Part 1: Change From Baseline in Body Temperature |
0.20; 0.02; -0.01; 0.09; 0.06; 0.01 | — |
| SECONDARY Part 2: Change From Baseline in Body Temperature |
0.19; 0.09; 0.13; 0.08; 0.03; 0.03 | — |
| SECONDARY Part 1: Change From Baseline in Heart Rate (12-Lead Electrocardiogram [ECG]) |
1.6; 1.0; 2.1; 2.5 | — |
| SECONDARY Part 2: Change From Baseline in Heart Rate (ECG) |
-1.0; -1.7; 1.7; 1.9 | — |
| SECONDARY Part 1: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval |
-7.3; -6.3; -5.5; -1.9; -0.5; -0.8 | — |
| SECONDARY Part 2: Change From Baseline in PR Interval, QRS Interval, QT Interval and QTcF Interval |
-3.2; -2.8; 1.2; 0.6; -1.4; -1.9 | — |
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 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 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.
Data sourced from ClinicalTrials.gov (NCT03555890). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.