Effect of Glucuronosyltransferase (UGT) Genetic Variation on Pharmacokinetics of Empagliflozin

Sponsor
Ain Shams University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05036421
Collaborator
(none)
18
1
1
2.5
7.3

Study Details

Study Description

Brief Summary

The aim of this works is to investigate the effect of genetic polymorphism of snps on human response to treatment with empagliflozin and its correlation with with pharmacokinetic parameters in Egyptian subjects

Condition or Disease Intervention/Treatment Phase
  • Drug: Empagliflozin 10 milligram
Phase 3

Detailed Description

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, therefore resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia and also assists weight loss and blood pressure reduction.

ABSORPTION Following oral administration, peak plasma concentrations were reached at 1.5 hours post-dose and then declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. Administration following a high-fat and high-calorie meal results in a slightly lower exposure with area under the curve (AUC) decreasing by approximately 16% and Cmax decreasing by approximately 37% compared to fasted condition.

METABOLISM In vitro studies suggest that empagliflozin is primarily metabolized by glucuronidation by 5'-diphospho-glucuronosyltransferases UG2B7, UGT1A3, UGT1A8, and UGT1A9. The most abundant metabolites are three glucuronide metabolites: 2-O-, 3-O-, and 6-O-glucuronide. Empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. It is a substrate for p-glycoprotein (p-gp), however in vitro studies suggest that it is unlikely to cause interactions with drugs that are p-gp substrates.

After oral administration, empagliflozin was 41.2% eliminated in feces and 54.4% eliminated in urine.

Terminal elimination half life was found to be 12.4 h based on population pharmacokinetic analysis.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
open label, single-dose, one-period, designopen label, single-dose, one-period, design
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Effect of UGT Genetic Variation on Pharmacokinetics of Empagliflozin
Anticipated Study Start Date :
Feb 15, 2022
Anticipated Primary Completion Date :
May 1, 2022
Anticipated Study Completion Date :
May 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Study Group

Empagliflozin

Drug: Empagliflozin 10 milligram
antihyperglycemic medication
Other Names:
  • Jardiance
  • Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetic parameters [48 hours]

      AUC0→∞

    2. Bioavailability parameters [24 hours]

      Cmax

    Secondary Outcome Measures

    1. Secondary outcome [48 hours]

      Tmax

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Healthy adult volunteers

    • Age between (18-45 years)

    • Normal BMI.

    • Understand the procedures and are willing to participate and gave their final written consent prior to the commencement of the study procedures.

    • The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests [hematology, clinical chemistry, urinalysis, serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody).

    Exclusion Criteria:
    • Treatment with any known enzyme-inducing/inhibiting agents within 30 days prior to the start of the study and throughout the study.

    • Subjects who have taken any medication less than two weeks of the trials starting date.

    • Susceptibility to allergic reactions to study drugs.

    • Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.

    • Gastrointestinal diseases.

    • Renal diseases.

    • Cardiovascular diseases.

    • Pancreatic disease including diabetes.

    • Hepatic diseases.

    • Hematological disease or pulmonary disease

    • Abnormal laboratory values.

    • Subjects who have donated blood or who have been involved in multiple dosing study requiring a large volume of blood (more than 500 ml) to be drawn within 6 weeks preceding the start of the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Faculty of Pharmacy Cairo Egypt

    Sponsors and Collaborators

    • Ain Shams University

    Investigators

    • Principal Investigator: Sara M Shaheen, Assiss. Prof, Ain Shams University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ain Shams University
    ClinicalTrials.gov Identifier:
    NCT05036421
    Other Study ID Numbers:
    • PHCL277
    First Posted:
    Sep 5, 2021
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ain Shams University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 8, 2022