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Trial record 10 of 66 for:    Levocetirizine

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

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ClinicalTrials.gov Identifier: NCT03555890
Recruitment Status : Completed
First Posted : June 14, 2018
Last Update Posted : September 21, 2018
Sponsor:
Collaborator:
Zensei Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Rhinitis Drug: Levocetirizine IRT 5 mg Drug: Levocetirizine ODT 5 mg Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 18, 2018
Actual Primary Completion Date : July 2, 2018
Actual Study Completion Date : September 17, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Levocetirizine IRT 5 mg
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).

Drug: Levocetirizine ODT 5 mg
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.

Experimental: 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.
Drug: Levocetirizine IRT 5 mg
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).

Drug: Levocetirizine ODT 5 mg
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.

Experimental: 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.
Drug: Levocetirizine IRT 5 mg
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).

Drug: Levocetirizine ODT 5 mg
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.

Experimental: 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.
Drug: Levocetirizine IRT 5 mg
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).

Drug: Levocetirizine ODT 5 mg
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.




Primary Outcome Measures :
  1. Area under plasma concentration-time curve (AUC) from zero hours to last time of quantifiable concentration (AUC [0-t]) of levocetirizine: Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2,3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-t).

  2. AUC (0-t) of levocetirizine: Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2,3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-t).

  3. Maximum plasma concentration (Cmax) of levocetirizine: Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Cmax

  4. Cmax of levocetirizine: Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Cmax


Secondary Outcome Measures :
  1. Number of subjects with adverse events (AE) and serious AE (SAE) in Part 1 [ Time Frame: Up to Day 18 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

  2. Number of subjects with AE and SAE in Part 2 [ Time Frame: Up to Day 18 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

  3. Number of subjects with abnormal hematology parameters: Part 1 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for hematology parameters will include Platelet count, hemoglobin, Red blood cell (RBC) count, hematocrit, RBC indices like mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and percentage reticulocytes. White blood cell (WBC) count with differential will include neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  4. Number of subjects with abnormal hematology parameters: Part 2 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for hematology parameters will include Platelet count, hemoglobin, RBC count, hematocrit, RBC indices like MCV, MCH and percentage reticulocytes. WBC count with differential will include neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  5. Number of subjects with abnormal clinical chemistry parameters: Part 1 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for clinical chemistry parameters will include blood urea nitrogen (BUN), potassium, calcium, sodium, creatinine, fasting glucose, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline phosphate, Gamma-glutamyl transferase (GGT), Creatine kinase (CK), Creatine phosphokinase (CPK), total cholesterol high-density lipoprotein (HDL), low-density lipoprotein (LDL), lactate dehydrogenase (LDH), uric acid, amylase, chloride, inorganic phosphorus, triglycerides, total protein, albumin, total and direct bilirubin.

  6. Number of subjects with abnormal clinical chemistry parameters: Part 2 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for clinical chemistry parameters will include BUN, potassium, calcium, sodium, creatinine, fasting glucose, AST, ALT, Alkaline phosphate, GGT, CK, CKP, total cholesterol, HDL, LDL, uric acid, amylase, chloride, inorganic phosphorus, triglycerides, total protein, albumin, total and direct bilirubin.

  7. Number of subjects with abnormal urinalysis parameters: Part 1 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for urinalysis will include specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen by dipstick, and microscopic examination if blood or protein is abnormal.

  8. Number of subjects with abnormal urinalysis parameters: Part 2 [ Time Frame: Up to Day 18 ]
    Laboratory assessment for urinalysis will include specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen by dipstick, and microscopic examination if blood or protein is abnormal.

  9. Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP): Part 1 [ Time Frame: Up to Day 18 ]
    Blood pressure will be measured in supine position after 5 minutes rest

  10. Change from Baseline in SBP and DBP: Part 2 [ Time Frame: Up to Day 18 ]
    Blood pressure will be measured in supine position after 5 minutes rest

  11. Change from Baseline in pulse rate: Part 1 [ Time Frame: Up to Day 18 ]
    Pulse rate will be measured in supine position after 5 minutes rest

  12. Change from Baseline in pulse rate: Part 2 [ Time Frame: Up to Day 18 ]
    Pulse rate will be measured in supine position after 5 minutes rest

  13. Change from Baseline in body temperature: Part 1 [ Time Frame: Up to Day 18 ]
    Body temperature will be measured in supine position after 5 minutes rest

  14. Change from Baseline in body temperature: Part 2 [ Time Frame: Up to Day 18 ]
    Body temperature will be measured in supine position after 5 minutes rest

  15. Change from Baseline in 12-lead Electrocardiogram (ECG): Part 1 [ Time Frame: Up to Day 18 ]
    Single 12-lead ECG will be obtained using an ECG machine that automatically measures heart rate, PR, QRS, QT, and QT interval corrected for heart rate (QTc) intervals.

  16. Change from Baseline in 12-lead ECG: Part 2 [ Time Frame: Up to Day 18 ]
    Single 12-lead ECG will be obtained using an ECG machine that automatically measures heart rate, PR, QRS, QT, and QTc intervals.

  17. AUC from time zero to infinity (AUC [0-inf]) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-inf)

  18. AUC (0-inf) of levocetirizine: Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-inf)

  19. Time to Cmax (Tmax) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Tmax

  20. Tmax of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Tmax

  21. Terminal elimination half-life (t 1/2) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of t 1/2

  22. T 1/2 of levocetirizine: Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of t 1/2

  23. Percentage of AUC (0-inf) obtained by extrapolation (percentage AUCex) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of percentage AUCex

  24. Percentage AUCex) of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of percentage AUCex

  25. Apparent clearance following oral dosing (CL/F) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of CL/F

  26. CL/F of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of CL/F

  27. Apparent volume of distribution after oral administration (Vz/F) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Vz/F

  28. Vz/F of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of Vz/F

  29. Elimination rate constant (kel) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of kel

  30. Kel of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of kel

  31. Mean residence time (MRT) of levocetirizine : Part 1 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of MRT

  32. MRT of levocetirizine : Part 2 [ Time Frame: Pre-dose and at 15 and 30 minutes, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 hours post-dose. ]
    Blood samples will be collected at indicated time points for analysis of MRT



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Healthy Japanese male subjects will be part of this study.
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03555890


Locations
Japan
GSK Investigational Site
Fukuoka, Japan, 812-0025
Sponsors and Collaborators
GlaxoSmithKline
Zensei Pharmaceutical Co., Ltd.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03555890     History of Changes
Other Study ID Numbers: 204706
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: September 21, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Oral disintegrating tablet
Levocetirizine
Immediate release tablet
Bioequivalence
Japanese subjects

Additional relevant MeSH terms:
Levocetirizine
Rhinitis
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Cetirizine
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Allergic Agents