Pharmacokinetic Evaluation of Empagliflozin

Pharmacokinetic Evaluation of Empagliflozin in Healthy Egyptian Volunteers Using LC-MS/MS: Compared With Other Ethnic Populations

Project PI (Principal Investigator): Dr Bassam Mahfouz Ayoub, Ph.D., Lecturer of Pharmaceutical Chemistry, The British University in Egypt.

Study Design The proposed study will consider the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers and the results will be compared with the other reported ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies, and to assess potential subgroup differences. The design of the study is open labeled, randomized, one treatment, one period, single dose pharmacokinetic study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Empagliflozin 25mg

Detailed Description

Study Design The proposed study will consider the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers and the results will be compared with the other reported ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies, and to assess potential subgroup differences. The design of the study is open labeled, randomized, one treatment, one period, single dose pharmacokinetic study. The main pharmacokinetic parameters which are Cmax, Tmax, t1/2, elimination rate constant, AUC0-t and AUC0-inf, will be estimated. Fasting of all volunteers will eliminate the possible interaction from food or caffeine consumption. The pharmacokinetic parameters of empagliflozin will be studied in healthy human subjects according to the ethical regulations of World Medical Association Declaration of Helsinki (October 1996) and the International Conference of Harmonisation Tripartite Guideline for Good Clinical Practice. Written informed consent was provided (attached and signed by the six volunteers) in order to be approved by the ethics committee of the Faculty of Pharmacy, The British University in Egypt. The good health of the human subjects was confirmed by a complete medical history and physical examination. Samples from six, healthy, adult, male, smoking, Egyptian volunteers (age: 22-33 years, Average weight: 77.8 kg, Average BMI: 29.2) will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 h, to be transferred to heparinized centrifuge tubes in order to be analyzed by LC-MS/MS study (developed & validated) after single oral dose administration of one Jardiance® tablet nominally containing 25 mg of empagliflozin. The blood samples (3 mL of each sample) will be centrifuged at 3000 rpm for 5 minutes, one mL of the plasma will be separated and spiked with 100 µL (equivalent to 100 ng) of internal standard working solution and then the sample preparation and LC-MS/MS determination will be applied. The main pharmacokinetic parameters of the study which are Cmax, Tmax, t1/2, elimination rate constant, AUC0-t and AUC0-inf will be estimated, using a validated excel software. Blood glucose level will be determined for all volunteers at different time intervals to monitor any hypoglycemic effect. The study will be conducted as per FDA guidelines. The development of such correlations between empagliflozin concentrations and its pharmacologic responses will enable clinicians to apply pharmacokinetic principles to actual patient situations. The evaluation of safety of the study will be based on monitoring of blood glucose level, vital signs, pulse rate, monitoring of adverse events, and physical examination.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 33 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The good health of the human subjects was confirmed by a complete medical history and physical examination.

Exclusion Criteria:

• Chronic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pharmacokinetic evaluation; Empagliflozin 25 mg	Drug: Empagliflozin 25mg; Samples from six, healthy, adult, male, smoking, Egyptian volunteers (age: 22-33 years, Average weight: 77.8 kg, Average BMI: 29.2) will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 h after administration of Empagliflozin 25 mg; Other Names: Jardiance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The peak plasma concentration of a drug after administration	12 Hours
Tmax	Time to reach Cmax.	12 Hours
Elimination half life	The time required for the concentration of the drug to reach half of its original value.	12 Hours
Elimination rate constant	The rate at which a drug is removed from the body.	12 Hours
Area under the curve	The integral of the concentration-time curve	12 Hours

Collaborators and Investigators

• Sponsor: British University In Egypt

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): February 2, 2017
• Study Completion (Actual): February 2, 2017

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: YIRG-2016-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Publication of data in a scientific journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes